bluuebunny/crossref_metadata_2025 huggingface dataset:
The females have spoken. A patient-centered national survey on the administration of emergent transfusions with the potential for future fetal harm
Authors: Uhlich Rindi , Hu Parker , Yazer Mark , Jansen Jan O. , Patrician Patricia , Marques Marisa B. , Reynolds Lindy , Fifolt Matthew , Stephens Shannon W. , Gelbard Rondi B. , Kerby Jeffrey , Holcomb John B.
Published: February 2023

Background

Traumatic hemorrhage is the leading cause of preventable death. Early in the resuscitation, only RhD-positive red blood cells are likely to be available, which poses a small risk of causing harm to a future fetus if transfused to an RhD-negative females of childbearing age (CBA), i.e., 15-49 years old. We sought to characterize how the population, in particular females of CBA, felt about emergency blood administration vis-a-vis potential future fetal harm.

Methods

National survey using Facebook advertisements in three waves from 01/2021 to 01/2022. The advertisements directed users to the survey site with 7 demographic questions and 4 questions on accepting transfusion with differing probabilities for future fetal harm (none/any/1:100/1:10,000). Acceptance of transfusion questions scored on 3-point Likert scale (likely/neutral/unlikely). Only completed responses by females were analyzed.

Results

Advertisements were viewed 16,600,430 times by 2,169,805 people with 15,396 advertisement clicks and 2,873 surveys initiated. Most (79%; 2,256/2,873) were fully completed. Majority (90%; 2,049/2,256) of respondents were female. 80% of females (1,645/2,049) were of CBA. Most females responded “likely” or “neutral” when asked whether they would accept a lifesaving transfusion if the following risk of fetal harm were present: no risk (99%); any risk (83%); 1:100 risk (85%); 1:10,000 risk (92%). There were no differences between females of CBA versus non-CBA with respect to the likelihood of accepting lifesaving transfusion with any potential for future fetal harm (p = 0.24).

Conclusion

This national survey suggests that most females would accept lifesaving transfusion even with the potential low risk of future fetal harm.

Level of Evidence

Prognostic and Epidemiological; Level 1
Surgical resident operative autonomy on nights and weekends: What happens to surgical education during off-hours?
Authors: Anjaria Devashish J. , Oliver Joseph B. , Yu Yasong , Tsui Grace , Kunac Anastasia , Livingston David H.
Published: February 2023

BACKGROUND

Surgical resident operative autonomy is critical for trainee maturation to independence. Acute care surgery (ACS) cases commonly occur off-hours and tension between operating room availability and on-call staff can affect resident operative autonomy. We examined operative resident autonomy for general, vascular, and thoracic (GVT) surgery during nights and weekends. We hypothesized that residents would be afforded less operative autonomy during off-hours than weekdays.

METHODS

This retrospective cohort study uses the Veterans Affairs Surgical Quality Improvement Program database, we examined all GVT cases at Veterans Affairs teaching hospitals from 2004 to 2019. All cases are coded for the level of supervision at the time of surgery: AP, attending primary surgeon; AR, attending and resident operating together; and RP, resident primary (attending supervising but not scrubbed). Cases starting between 6 pm to 7 am Monday through Friday were considered nights, cases on Saturday/Sunday were considered weekends, and collectively considered “off-hours.” Resident primary case rates were compared by start time and type.

RESULTS

Over the 15-year study period, there were 666,421 GVT cases performed with 38,097 cases (6%) performed off-hours. During off-hours, 31,396 (83%) were ACS compared with 5% of daytime cases. Overall, off-hours cases have higher RP rate than daytime cases (6.8% vs. 5.8%, p < 0.001). Daytime ACS cases have higher rates of RP than nights/weekends (7.6% vs. 6.8%, p < 0.001). Conversely, daytime elective cases have lower RP than nights (5.7% vs. 7.9%, p < 0.001). During off-hours, there are more RP cases on nights compared with weekends (7.1% vs. 6.5%, p = 0.02).

CONCLUSION

Overall, residents were afforded more operative autonomy during off-hours, with nights having greater RP than weekends. In contrast, ACS cases have more autonomy during weekdays. These data have potentially significant implications for ACS service staffing, night float rotations, and overall resident operative experience on ACS services.

LEVEL OF EVIDENCE/STUDY TYPE

Prognostic and Epidemiological; Level III.
Proteomics: Its Promise and Pitfalls in Shaping Precision Medicine in Solid Organ Transplantation
Authors: Farkona Sofia , Pastrello Chiara , Konvalinka Ana
Published: February 2023

Solid organ transplantation is an established treatment of choice for end-stage organ failure. However, all transplant patients are at risk of developing complications, including allograft rejection and death. Histological analysis of graft biopsy is still the gold standard for evaluation of allograft injury, but it is an invasive procedure and prone to sampling errors. The past decade has seen an increased number of efforts to develop minimally invasive procedures for monitoring allograft injury. Despite the recent progress, limitations such as the complexity of proteomics-based technology, the lack of standardization, and the heterogeneity of populations that have been included in different studies have hindered proteomic tools from reaching clinical transplantation. This review focuses on the role of proteomics-based platforms in biomarker discovery and validation in solid organ transplantation. We also emphasize the value of biomarkers that provide potential mechanistic insights into the pathophysiology of allograft injury, dysfunction, or rejection. Additionally, we forecast that the growth of publicly available data sets, combined with computational methods that effectively integrate them, will facilitate a generation of more informed hypotheses for potential subsequent evaluation in preclinical and clinical studies. Finally, we illustrate the value of combining data sets through the integration of 2 independent data sets that pinpointed hub proteins in antibody-mediated rejection.
Influence of Tricuspid Regurgitation After Heart Transplantation: A Single-center Experience
Authors: Krey Rebecca , Sommer Wiebke , Meyer Anna , Rivinius Rasmus , Schlegel Philipp , Frey Norbert , Karck Matthias , Warnecke Gregor , Arif Rawa
Published: February 2023

Background.

Tricuspid valve regurgitation (TVR) is often observed after orthotopic heart transplantation. However, there is a scarcity of data regarding long-term outcomes of patients with TVR.

Methods.

Between January 2008 and December 2015, 169 patients underwent orthotopic heart transplantation at our center and were included in this study. TVR trends and associated clinical parameters were retrospectively analyzed. TVR was assessed after 30 d, 1 y, 3 y, and 5 y, and groups were defined according to changes in TVR grade: constant (group 1; n = 100), improvement (group 2; n = 26), and deterioration (group 3; n = 43). Survival, outcome with regard to operative technique, and long-term kidney and liver function during follow-up were assessed.

Results.

Mean follow-up time was 7.67 ± 4.17 y (median 8.62, Q1 5.06, Q3 11.16). Overall mortality was 42.0%, with differences between the groups (P < 0.01). Cox regression analysis revealed improvement of TVR as a significant predictor for survival (hazard ratio 0.23; 95% confidence interval, 0.08-0.63, P < 0.01). After 1 y 2.7%, after 3 y 3.7%, and after 5 y 3.9% of the patients showed persistent severe TVR. Creatinine levels after 30 d and 1, 3, and 5 y showed significant differences between the groups (P = 0.02, P < 0.01, P < 0.01, and P = 0.01), deterioration of TVR being associated with higher creatinine levels during follow-up.

Conclusions.

Deterioration of TVR is associated with higher mortality and renal dysfunction. Improvement of TVR may function as a positive predictor for long-term survival after heart transplantation. Improvement of TVR should be a therapeutic goal offering a prognostic value for long-term survival.
Efficacy of Behavioral Interventions for Urinary Incontinence Among Women Residing in Nursing Homes
Authors: Allen Lindsay M. , Nalley Chelsea , Devries Alison R. , Fisher Steve R.
Published: February 2023

PURPOSE:

The purpose of this systematic review was to summarize recent evidence on the efficacy of behavioral interventions for the management of urinary incontinence (UI) among women in nursing homes.

METHODS:

Systematic review of the literature. For this review, behavioral interventions were defined as those that included some form of physical exercise or behavior modification such as scheduled toileting.

SEARCH STRATEGY:

A search of MEDLINE/PubMed, CINAHL, Scopus, and Cochrane Library electronic databases was conducted seeking randomized controlled trials published since 2010 in female participants residing in long-term care facilities (nursing homes, skilled nursing facilities) and diagnosed with UI. Inclusion criteria were studies that addressed the effects of voiding regimens, lower extremity strengthening, functional training, food and fluid management, and pelvic floor muscle training. Independent reviewers extracted relevant data and assessed methodological quality using the PEDro scale.

FINDINGS:

Five studies (pooled sample, N = 399) met inclusion criteria; mean age of participants was 81.1 ± 6.8 years; 85% were female. The PEDro scores ranged from 6 to 9; only 2 studies included residents with cognitive impairment. Interventions included voiding strategies, increasing physical activity, functional mobility training, pelvic floor muscle training, fluid management, and multicomponent combinations of approaches. Three of the 5 studies were multicomponent interventions and 2 focused on a single intervention. Outcomes included objective measures of incontinent episodes and subjective assessments of UI severity.

CONCLUSIONS:

Behaviorally based interventions can be successful in improving UI among nursing residents with and with no cognitive impairment.

IMPLICATIONS:

Future studies should examine logistic and labor costs associated with sustaining behavioral interventions using nursing home staff and investigate the effects of these therapies using appropriate quality-of-life metrics for this population.
Prospective, Case-Control Study Evaluating Effects of No-Sting Liquid Barrier Film on Skin Condition and Maturation of Stratum Corneum in Premature Neonates
Authors: Boyar Vita , Desai Tuisha
Published: February 2023

PURPOSE:

To assess effects of a no-sting liquid barrier film (NSLBF) on the skin condition and maturation of the stratum corneum in premature neonates.

DESIGN:

This was a prospective, case-control study with each subject serving as their own control.

SUBJECTS AND SETTING:

The sample comprised 33 neonates, between 23 and 32 weeks of gestational age (GA). Participants received care in a level 4 neonatal intensive care unit in the northeastern United States. Data were collected between May 2018 and May 2019.

METHODS:

All participants had NSLBF applied to their left chest, left abdomen, and left anterior and posterior upper thigh. The right side was left untreated and served as self-control. Measurements of skin pH, hydration, transepidermal water loss (TEWL) and Neonatal Skin Condition Scores were obtained on both the untreated right and treated left sides of the body over a 14-day period on days 1, 3, 7, and 14.

RESULTS:

Worsening skin condition scores were observed on the treated side on days 7 and 14. There was an improvement in TEWL on the treated side, manifested as decrease in TEWL values. There was no difference in pH. At all points in time hydration was lower on the treated side.

CONCLUSIONS:

Worsening skin condition scores and hydration status on the treated side indicate an altered or delayed process of skin maturation. These findings suggest that no-sting liquid barrier (NSLB) application should be limited to skin under medical devices, dressings, tapes, and affected areas. In addition, we recommend allowing adequate intervals to allow physiologic stratum corneum maturation between applications of NSLB.
The Impact of Diabetic Foot Ulcer on Individuals' Lives and Daily Routine
Authors: Costa Idevania G. , Camargo-Plazas Pilar
Published: February 2023

PURPOSE:

The purpose of this study was to explore the impact of diabetic foot ulcer (DFU) on individuals' lives and daily routines.

DESIGN:

Qualitative design informed by social constructivism and symbolic interactionism frameworks.

SUBJECTS AND SETTING:

The sample comprised 30 individuals attending a wound care clinic in Southeast Ontario, Canada. Most participants (n = 17) were between the ages of 65 and 92 years, were male (n = 20), married (n = 21), living with their family (n = 23), and had completed high school (n = 26).

METHODS:

One-to-one semistructured interviews were conducted by the first author until saturation of each emerging theme was achieved. Interviews were audio-recorded and lasted from 45 to 90 minutes. Data collection and analysis occurred simultaneously and included intensive semistructured interviews, field notes, and researcher's journal.

RESULTS:

Participants with DFUs were found to perceive a “sense of life change,” impacting their lives across physical, psychological, and social spheres. They reported 4 key themes indicating that DFUs were (1) limiting their outings; (2) restricting leisure activities; (3) impacting personal and social life; and (4) contributing to emotional fluctuations.

CONCLUSION:

Sense of life changes resulting from DFUs were associated with participant reporting loss of freedom and enjoyment. These findings underscore the need for holistic support for patients with DFUs that simultaneously address physical, psychological, and social needs and areas of impact.
Effect of a Hospital-Acquired Pressure Injury (HAPI) Risk Score on HAPI Rates in Patients With Vascular Diseases
Authors: Moyse Tonya , Bates Jacqueline , Bena James F. , Morrison Shannon L. , Albert Nancy M.
Published: February 2023

PURPOSE:

The purpose of this study was to assess whether a validated hospital-acquired pressure injury (HAPI) risk scale and best practice interventions were associated with lower HAPI rates compared with previous care. We also sought to identify a cut score of HAPI risk when using the instrument.

DESIGN:

Nonequivalent 2-group pre- and postintervention comparative study.

SUBJECTS AND SETTING:

The sample comprised 2871 patients treated for vascular diseases; data were collected on 2674 patients before the intervention and 197 patients postintervention. Their mean (SD) age was 69.3 (12.4) years; 29.3% (n = 842) had a history of diabetes mellitus. Based on discharge status, more patients received home health care after discharge in the postintervention group, 34% (n = 67/197) versus 16.2% (n = 430/2662), P = .001. The study setting was a quaternary care hospital in the Midwestern United States.

METHODS:

Patients who were at high risk for HAPI, based on a nomogram score, received a mobility and ambulation program intervention. Pre- and postintervention cohorts were compared using analysis of variance, χ2 test, and Fisher exact test. A receiver operating characteristic curve plot was generated to determine the ability of the risk score tool to identify HAPI risk at all possible cut points.

RESULTS:

Despite differences in patient characteristics, primary medical diagnosis, and postdischarge health care needs, the HAPI rate decreased postintervention from 13.8% (n = 370/2674) to 1.5% (n = 3/197), P = .001. A HAPI risk-predicted value cut score of 18 had strong sensitivity (0.81) and specificity (0.81), and positive and negative predictive values of 0.42 and 0.96, respectively.

CONCLUSION:

Despite higher patient acuity during the intervention period, HAPI rate decreased after HAPI nomogram and nurse-led mobility intervention implementation.
A pillar/perfusion plate enhances cell growth, reproducibility, throughput, and user friendliness in dynamic 3D cell culture
Authors: Lekkala Vinod Kumar Reddy , Kang Soo-Yeon , Liu Jiafeng , Shrestha Sunil , Acharya Prabha , Joshi Pranav , Zolfaghar Mona , Lee Minseong , Jamdagneya Paarth , Pagnis Sohan , Kundi Arham , Kabbur Samarth , Kim Ung Tae , Yang Yong , Lee Moo-Yeal
Published: February 2023

Static three-dimensional (3D) cell culture has been demonstrated in ultralow attachment well plates, hanging droplet plates, and microtiter well plates with hydrogels or magnetic nanoparticles. Although it is simple, reproducible, and relatively inexpensive, thus potentially used for high-throughput screening, statically cultured 3D cells often suffer from the necrotic core due to limited nutrient and oxygen diffusion and waste removal and have limitedin vivo-like tissue structure. Here, we overcome these challenges by developing a pillar/perfusion plate platform and demonstrating high-throughput, dynamic 3D cell culture. Cell spheroids have been loaded on the pillar plate with hydrogel by simple sandwiching and encapsulation and cultured dynamically in the perfusion plate on a digital rocker. Unlike traditional microfluidic devices, fast flow rates were maintained within perfusion wells, and the pillar plate could be separated from the perfusion plate for cell-based assays. It was compatible with common lab equipment and allowed cell culture, testing, staining, and imagingin situ.The pillar/perfusion plate enhanced cell growth by rapid diffusion, reproducibility, assay throughput, and user friendliness in dynamic 3D cell culture.
The drivers of dark diversity in the Scandinavian tundra are metric-dependent
Authors: Hostens Lore , Van Meerbeek Koenraad , Wiegmans Dymphna , Larson Keith , Lenoir Jonathan , Clavel Jan , Wedegärtner Ronja , Pirée Amber , Nijs Ivan , Jonas J. Lembrechts
Published: February 2023

Aim

Dark diversity refers to the set of species that are not observed in an area but could potentially occur based on suitable local environmental conditions. In this paper, we applied both niche-based and co-occurrence-based methods to estimate the dark diversity of vascular plant species in the subarctic tundra. We then aimed to unravel the drivers explaining (1) why some locations were missing relatively more suitable species than others, and (2) why certain plant species were more often absent from suitable locations than others.

Location

The Scandinavian tundra around Abisko, northern Sweden.

Methods

We calculated the dark diversity in 107 plots spread out across four mountain trails using four different methods. Two niche-based (Beals’ index and hypergeometric method) and two co-occurrences-based (climatic niche model and climatic niche model followed by species-specific threshold) methods. This was then followed by multiple generalized linear mixed models and general linear models to determine which habitat characteristics and species traits contributed most to the dark diversity.

Results

The study showed a notable divergence in the predicted drivers of dark diversity depending on the method used. Nevertheless, we can conclude that plot-level dark diversity was generally 18% higher in areas at low elevations and 30% and 10% higher in areas with a low species richness or low levels of habitat disturbance, respectively.

Conclusion

Our findings call for caution when interpreting statistical findings of dark diversity estimates. Even so, all analyses point towards an important role for natural processes such as competitive dominance as main driver of the spatial patterns found in dark diversity in the northern Scandes.
Delayed development of basal spikelets in wheat explains their increased floret abortion and rudimentary nature
Authors: Backhaus Anna Elisabeth , Griffiths Cara , Vergara-Cruces Angel , Simmonds James , Lee Rebecca , Morris Richard J. , Uauy Cristobal
Published: February 2023

Wheat (Triticum aestivum L.) breeding efforts have increased grain yield predominantly by raising grain numbers per spikelet, rather than grain weight or spikelet number. However, across a single spike large differences exist in the number of grains per spikelet. The central spikelets produce the highest number of grains in any given genotype while apical and basal spikelets are less productive. Basal spikelets are delayed in development just after initiation and are smaller and less advanced than central spikelets already by the glume primordium stage. However, basal spikelets continue to develop and produce florets until much later in the wheat growth cycle. The precise timings or the cause of their growth cessation, and subsequent abortion, is largely unknown. In this study we investigated the underlying causes of rudimentary basal spikelet abortion. We investigated basal spikelet development in four UK winter wheat varieties as well as a set of near-isogenic lines forVRT-A2(VEGETATIVE TO REPRODUCTIVE TRANSITION 2) using shading applications in the field. We propose that basal spikelet abortion is likely the consequence of complete floret abortion as both occur at the same time and have the same response to shading treatments. Furthermore, we found that the developmental age of florets pre-abortion is an important factor for their likelihood to survive and develop viable seed. Previously, it had been proposed that reduced assimilate availability in the base of the spike leads to increased abortion. Re-analysis of published data alongside data presented here, however, does not support this model. We found that rather than assimilate availability, it is the reduced developmental age of basal florets before abortion that correlates with increased abortion. Using the floret Waddington developmental stage pre-abortion, we were able to predict final grain set per spikelet across the spike, alongside the characteristic gradient in number of grains from basal to central spikelets. We found that advancing past Waddington stage 5.5 seems to be important for floret survival and that most florets in basal spikelets had not reached this stage at the onset of floret abortion. The abortion of all florets could therefore be the reason for their rudimentary appearance in the mature spike, suggesting that basal spikelet abortion is simply the consequence of all florets inside the spikelet being aborted and thus all other spikelet structures (e.g., lemma, rachilla, glume) also ceasing to develop. Future efforts to improve spikelet homogeneity across the spike could thus focus on improving basal spikelet establishment and increasing floret development rates pre-abortion.
Conformational analysis of chromosome structures reveals vital role of chromosome morphology in gene function
Authors: Zhan Yuxiang , Yildirim Asli , Boninsegna Lorenzo , Alber Frank
Published: February 2023

The 3D conformations of chromosomes are highly variant and stochastic between single cells. Recent progress in multiplexed 3D FISH imaging, single cell Hi-C and genome structure modeling allows a closer analysis of the structural variations of chromosomes between cells to infer the functional implications of structural heterogeneity. Here, we introduce a two-step dimensionality reduction method to classify a population of single cell 3D chromosome structures, either from simulation or imaging experiment, into dominant conformational clusters with distinct chromosome morphologies. We found that almost half of all structures for each chromosome can be described by 5-10 dominant chromosome morphologies, which play a fundamental role in establishing conformational variation of chromosomes. These morphologies are conserved in different cell types, but vary in their relative proportion of structures. Chromosome morphologies are distinguished by the presence or absence of characteristic chromosome territory domains, which expose some chromosomal regions to varying nuclear environments in different morphologies, such as nuclear positions and associations to nuclear speckles, lamina, and nucleoli. These observations point to distinct functional variations for the same chromosomal region in different chromosome morphologies. We validated chromosome conformational clusters and their associated subnuclear locations with data from DNA-MERFISH imaging and single cell sci-HiC data. Our method provides an important approach to assess the variation of chromosome structures between cells and link differences in conformational states with distinct gene functions.
Extruding transcription elongation loops observed in high-resolution single-cell 3D genomes
Authors: Wu Honggui , Zhang Jiankun , Tan Longzhi , Xie X. Sunney
Published: February 2023

Inside human nuclei, genes are transcribed within a highly packed genome, whose organization is facilitated by cohesin-mediated loop extrusion. However, whether cohesin-mediated loop extrusion participates in transcription is unknown. Here we report that the cohesin-mediated loop extrusion participates in transcription by forming a topoisomerases-regulated transcription elongation loop (TEL), in which cohesin is stalled at the transcription start site (TSS) and gradually extrudes loops asymmetrically until reaching the transcription termination site (TTS). By improving the spatial resolution of single-cell 3D genome mapping to 5 kb with micrococcal nuclease (MNase) in our new single-cell Micro-C (scMicro-C) method, we directly observed the loop expansion of TELs. Furthermore, TEL’s biological function is to ensure high transcriptional burst frequencies by fast re-initiation of RNA Pol II.

One-Sentence Summary

Single-cell high-resolution 3D genome structures reveal that cohesin-mediated loop extrusion participates in transcription.
Machine learning inference of continuous single-cell state transitions during myoblast differentiation and fusion
Authors: Shakarchy Amit , Zarfati Giulia , Hazak Adi , Mealem Reut , Huk Karina , Ziv Tamar , Avinoam Ori , Zaritsky Assaf
Published: February 2023

Cells modifying their internal organization during continuous state-transitions, supporting functions from cell division to differentiation. However, tools to measure dynamic physiological states of individual transitioning cells are lacking. We combined live-cell imaging and machine learning to monitor ERK1/2-inhibited primary murine skeletal muscle precursor cells, that transition rapidly and robustly from proliferating myoblasts to post-mitotic myocytes and then fuse, forming multinucleated myotubes. Our model, trained using motility and actin intensity features from single cell tracking data, effectively tracked real-time continuous differentiation, revealing that differentiation occurs 7.5-14.5 hours post-induction, followed by fusion ∼3 hours later. Co-inhibition of ERK1/2 and p38 led to differentiation without fusion. Our model inferred co-inhibition leads to terminal differentiation, indicating that p38 is specifically required for transitioning from terminal differentiation to fusion. Our model also predicted that co-inhibition leads to changes in actin dynamics. Mass spectrometry supported these in silico predictions and suggested novel fusion and maturation regulators downstream of differentiation. Collectively, this approach can be adapted to various biological processes to uncover novel links between dynamic single-cell states and their functional outcomes.
Cardiac Development Long non-coding RNA (CARDEL) is activated during human heart development and contributes to cardiac specification and homeostasis
Authors: Pereira Isabela T. , Gomes-Júnior Rubens , Hansel-Frose Aruana , Liu Man , Soliman Hossam A.N. , Chan Sunny S.K. , Dudley Samuel C. , Kyba Michael , Dallagiovanna Bruno
Published: February 2023

Successful heart development depends on the careful orchestration of a network of transcription factors and signaling pathways. In recent years, thein vitrocardiac differentiation using human pluripotent stem cells (hPSCs) has been used to uncover the intricate gene network regulation involved in the proper formation and function of the human heart. Here, we searched for uncharacterized cardiac developmental genes by combining a temporal evaluation of the human cardiac specificationin vitrowith the analysis of fetal and adult heart tissue gene expression. We discovered thatCARDEL(CARdiac DEvelopment Long non-coding RNA; LINC00890; SERTM2) expression coincides with the commitment to the cardiac lineage.CARDELknockout hPSCs differentiated poorly in cardiac cells, and hPSC-derived cardiomyocytes showed faster beating rates afterCARDELcontrolled overexpression during differentiation. Altogether, we demonstrate physiological and molecular evidence thatCARDELexpression contributes to sculpting the cardiac program during cell-fate commitment.
Evolution of promoter-proximal pausing enabled a new layer of transcription control
Authors: Chivu Alexandra G. , Basso Brent A. , Abuhashem Abderhman , Leger Michelle M. , Barshad Gilad , Rice Edward J. , Vill Albert C. , Wong Wilfred , Chou Shao-Pei , Chovatiya Gopal , Brady Rebecca , Smith Jeramiah J. , Wikramanayake Athula H. , Arenas-Mena César , Brito Ilana L. , Ruiz-Trillo Iñaki , Hadjantonakis Anna-Katerina , Lis John T. , Lewis James J. , Danko Charles G.
Published: February 2023

Promoter-proximal pausing of RNA polymerase II (Pol II) is a key regulatory step during transcription. Despite the central role of pausing in gene regulation, we do not understand the evolutionary processes that led to the emergence of Pol II pausing or its transition to a rate-limiting step actively controlled by transcription factors. Here we analyzed transcription in species across the tree of life. Unicellular eukaryotes display a slow acceleration of Pol II near transcription start sites that transitioned to a longer-lived, focused pause in metazoans. This event coincided with the evolution of new subunits in the NELF and 7SK complexes. Depletion of NELF in mammals shifted the promoter-proximal buildup of Pol II from the pause site into the early gene body and compromised transcriptional activation for a set of heat shock genes. Our work details the evolutionary history of Pol II pausing and sheds light on how new transcriptional regulatory mechanisms evolve.
Microcalcifications can either trigger or suppress breast precancer malignancy potential according to the mineral type in a 3D tumor model
Authors: Cohen Amit , Gotnayer Lotem , Aranovich Dina , Vidavsky Netta
Published: February 2023

Most early breast precancer lesions, termed ductal carcinomain situ(DCIS), contain microcalcifications (MCs), which are calcium-containing pathological minerals. The most common type of MCs is calcium phosphate crystals, mainly carbonated apatite; it is associated with either benign or malignant lesions.In-vitrostudies indicate that the crystal properties of apatite MCs can affect breast cancer progression. A less common type of MCs is calcium oxalate dihydrate (COD), which is almost always found in benign lesions. We developed a 3D tumor model of multicellular spheroids of human precancer cells containing synthetic MC analogs that link the crystal properties of MCs with the progression of breast precancer to invasive cancer. We show that apatite crystals induce proliferation and Her2 overexpression in DCIS cells. This tumor-triggering effect is increased when the carbonate fraction in the MCs decreases. COD crystals, in contrast, do not induce proliferation and reduce Her2 expression, even compared with control spheroids with no added MC analogs. This finding suggests that COD is not randomly located only in benign lesions—it may actively contribute to suppressing precancer progression in its surroundings. Our model provides an easy-to-manipulate platform to better understand the interactions between breast precancer cells and MCs. A better understanding of the effect of the crystal properties of MCs on precancer progression will potentially provide new directions for better precancer prognosis and treatment.
Synthesis and crystal structures of new chiral 3-amino-2H-azirines and the Pd complex of one of them
Authors: Linden Anthony , Bucher Christoph B. , Gubler Ralf , Villalgordo José M. , Heimgartner Heinz
Published: February 2023

3-Amino-2H-azirines are potentially versatile building blocks in heterocyclic and peptide synthesis. Three new 3-amino-2H-azirines have been synthesized as racemates or mixtures of diastereoisomers in cases where another chiral residue is incorporated as the exocyclic amine. The crystal structures of two of them, an approximately 1:1 diastereoisomeric mixture of (2R)- and (2S)-2-ethyl-3-[(2S)-2-(1-methoxy-1,1-diphenylmethyl)pyrrolidin-1-yl]-2-methyl-2H-azirine, C23H28N2O, 11, and 2-benzyl-3-(N-methyl-N-phenylamino)-2-phenyl-2H-azirine, C22H20N2, 12, and the third as its diastereoisomeric trans-PdCl2 complex, trans-dichlorido[(2R)-2-ethyl-2-methyl-3-(X)-2H-azirine][(2S)-2-ethyl-2-methyl-3-(X)-2H-azirine]palladium(II), where X = N-{[(1S,2S,5S)-6,6-dimethylbicyclo[3.1.1]heptan-2-yl]methyl}-N-phenylamino, [PdCl2(C21H30N2)2], 14, have been determined and the geometries of the azirine rings compared with those of 11 other 3-amino-2H-azirine structures reported in the literature. Most notable is the very long formal N—C single bond, which is, with one exception, around 1.57 Å. Each compound has crystallized in a chiral space group. The Pd atom in the trans-PdCl2 complex is coordinated by one of each of the pair of diastereoisomers, while both of the diastereoisomers share the same crystallographic site in the structure of 11; this property thereby manifesting itself as disorder. The chosen crystal of 12 is either an inversion twin or composed of a pure enantiomorph, but this could not be established specifically.
Private Equity Buyouts and Exports: The Impact of Brexit on UK Firms
Authors: Lavery Paul , Serena Jose‐Maria , Spaliara Marina‐Eliza , Tsoukas Serafeim
Published: February 2023

This paper examines how private equity (PE) buyouts affect export activity among target firms around the Brexit period. Using data on UK firms for 2012–2019 and difference‐in‐differences estimations for matched target versus non‐target firms, we assess how the unprecedented Leave vote affects portfolio firms' internationalization. We find that following the referendum, PE buyout targets are more likely to engage in exporting and are in turn more likely to increase the value of their exports and their export intensity relative to their non‐PE‐backed peers. We further find evidence of an active governance channel, whereby the benefits of PE investment after Brexit are more potent when greater governance changes occur on boards of directors, and for firms whose senior directors have more international experience.
Purtscher‐like retinopathy associated with systemic lupus erythematosus treated with rituximab plus low‐dose interleukin‐2: A case report
Authors: Li Min , Jin Yuebo , He Jing
Published: February 2023

Purtscher‐like retinopathy, an occlusive microvasculopathy, is a rare and severe ophthalmic complication of systemic lupus erythematosus (SLE) characterized by a sudden loss of vision with retinal whitening, cotton wool spots and minimal intraretinal hemorrhage. Recovery in visual acuity is usually poor even with prompt treatment. This case showed a patient with SLE concurrent Purtscher‐like retinopathy treated with rituximab and interleukin‐2 (IL‐2) with good prognosis. A 16‐year‐old female with a 2‐year history of SLE was admitted because of unrelieved disease activity of SLE when treated with a high dose of corticosteroids and immunosuppressants and she further suffered from reduced visual acuity in both eyes. She was diagnosed with Purtscher‐like retinopathy secondary to SLE after ocular examination. Rituximab and low‐dose IL‐2 for systemic treatment and intravitreal injection of anti‐vascular endothelial growth factor antibody to right eye were given. The SLE disease was completely relieved with the sight recovering and no recurrence of Purtscher‐like retinopathy was reported during 6‐year follow‐up. Purtscher‐like retinopathy associated with SLE should be treated early and promptly. Rituximab should be considered in SLE patients with Purtscher‐like retinopathy who have an incomplete response to initial immunosuppressive therapy and low‐dose IL‐2 may help induction of clinical remission.
Mechanical ventilation post‐bilateral lung transplantation: A scoping review
Authors: Morgan Stephen , Aneman Anders , Nair Priya
Published: February 2023

Background

Evidence from lung protective ventilation (LPV) in the acute respiratory distress syndrome has commonly been applied to guide periprocedural ventilation in lung transplantation. However, this approach may not adequately consider the distinctive features of respiratory failure and allograft physiology in the lung transplant recipient.

This scoping review was conducted to systematically map the research describing ventilation and relevant physiological parameters post‐bilateral lung transplantation with the aim to identify any associations with patient outcomes and gaps in the current knowledge base.

Methods

To identify relevant publications, comprehensive literature searches of electronic bibliographic databases were conducted with the guidance of an experienced librarian in MEDLINE, EMBASE, SCOPUS and the Cochrane Library. The search strategies were peer‐reviewed using the PRESS (Peer Review of Electronic Search Strategies) checklist. The reference lists of all relevant review articles were surveyed.

Publications were included in the review if they described relevant ventilation parameters in the immediate post‐operative period, published between 2000 and 2022 and involved human subjects undergoing bilateral lung transplantation. Publications were excluded if they included animal models, only single‐lung transplant recipients or only patients managed with extracorporeal membrane oxygenation.

Results

A total of 1212 articles were screened, 27 were subject to full‐text review and 11 were included in the analysis. The quality of the included studies was assessed to be poor with no prospective multi‐centre randomised controlled trials. The frequency of reported retrospective LPV parameters was as follows: tidal volume (82%), tidal volume indexed to both donor and recipient body weight (27%) and plateau pressure (18%). Data suggest that undersized grafts are at risk of unrecognised higher tidal volume ventilation indexed to donor body weight. The most reported patient‐centred outcome was graft dysfunction severity in the first 72 h.

Conclusion

This review has identified a significant knowledge gap that indicates uncertainty regarding the safest ventilation practice in lung transplant recipients. The risk may be greatest in patients with established high‐grade primary graft dysfunction and undersized allografts, and these factors may define a sub‐group that warrants further investigation.
Enabling social care services for older adults during periods of long‐term social isolation: Service provider perspectives
Authors: Budrikis Amy , Parry Cate , Adams Claire , Gringart Eyal , Sim Moira , McAullay Daniel , Strobel Natalie
Published: February 2023

Objective

To investigate how small, local organisations were impacted by and responded to COVID‐19 in their delivery of social care services to older adults (70 years and older). Lessons learnt and future implications are discussed.

Methods

Six representatives from four social care services (five females and one male) participated in individual semistructured interviews. Responses were analysed thematically.

Results

The key themes identified were service providers' experience, perceived needs of older adults and adapting services. Service providers positioned themselves as front‐line essential workers for their older adult clients, resulting in some emotional toll and distress for the service providers. They provided information, wellness checks and at‐home assistance to keep their older adult clients connected.

Conclusions

Service providers feel more prepared for future restrictions but flag the potential of training and supporting older adults to use technology to stay connected, as well as the need for more readily available funding to allow services to adapt quickly during times of crisis.
Using input–output models to estimate sectoral effects of carbon tax policy: Applications of the NGFS scenarios
Authors: Kay David , Jolley G. Jason
Published: February 2023

The Network of Central Banks and Supervisors for Greening the Financial System (NGFS) has engaged in scenario analysis that estimates a $200/ton carbon tax would be required to transition to net zero carbon by 2050. Using a $200/ton carbon tax as a base, this paper uses input–output (IO) modeling to generate price and revenue effects of a carbon tax. Results from these models, which can only be interpreted as the short‐run, upper‐bound effects of the carbon tax policy, imply that in response to a $200/ton tax on CO2e emissions, carbon‐intensive industries, such as agriculture, extraction, transportation, utilities, and chemicals, may experience price increases in the range of 10‐30 percent. Other industries will also experience price increases, but to a lesser degree, due to increased input costs associated with the tax. In addition, modeling results also suggest that industries facing elastic pricing regimes may face similar‐sized declines in revenues as a consequence of the carbon tax. Rank‐ordered impact results from these models can be utilized by bank supervisors and firms to adequately plan for sectoral‐level transition risk within their lending and/or investment portfolios.
“Never Look Back, Always Look Forward”: The Early Life of Nancy Power
Authors: Wickes Judi , Ellinghaus Katherine
Published: February 2023

This article examines of the life of Nancy Verna Power, an Aboriginal woman born in north‐west Queensland in 1910. Nancy Power was given an exemption certificate in 1933. The certificate released her from control by the Department of Native Affairs in 1933 and led her to remain silent about her identity in the later years of her life. This article examines Nancy's early life as a domestic servant, when she was under the control of the Chief Protector, the superintendent of Purga Mission and other government administrators. Using Phillips and Bunda's principles of “storying” each author describes a period of Nancy's life with an eye to their own connection to, and ability to tell, the story. Judi Wickes, Nancy's niece, tells her story from 1910 to 1924 and from 1934 to 1950 using family records and her own memories. Katherine Ellinghaus, a non‐Indigenous historian, uses the official written records created by the Queensland government to describe Nancy's life between 1930 and 1934.
Does lithium poisoning induce brain injuries?—A histopathological rat study
Authors: Klein Mathieu , Naffaa Vanessa , Chevillard Lucie , Risède Patricia , Saubaméa Bruno , Adle‐Biassette Homa , Mégarbane Bruno
Published: February 2023

Due to a narrow therapeutic index, prolonged lithium treatment and overdose may result in neurotoxicity. Neurotoxicity is deemed reversible with lithium clearance. However, echoing the report of syndrome of irreversible lithium‐effectuated neurotoxicity (SILENT) in rare severe poisonings, lithium‐induced histopathological brain injuries including extensive neuronal vacuolization, spongiosis and ageing‐like neurodegenerative changes were described in the rat following acute toxic and pharmacological exposure. We aimed to investigate the histopathological consequences of lithium exposure in rat models mimicking prolonged treatment and all three patterns of acute, acute‐on‐chronic and chronic poisonings observed in humans. We performed histopathology and immunostaining‐based analyses using optic microscopy of brains obtained from male Sprague–Dawley rats randomly assigned to lithium or saline (controls) and treated according to the therapeutic or to the three poisoning models. No lesion was observed in any brain structure in any of the models. Neuron and astrocyte counts did not differ significantly between lithium‐treated rats and controls. Our findings support that lithium‐induced neurotoxicity is reversible and brain injury not a common feature of toxicity.
Implant survival in the anterior mandible: A retrospective cohort study
Authors: Pedrinaci Ignacio , Sun Teresa Chanting , Sanz‐Alonso Mariano , Sanz‐Esporrin Javier , Hamilton Adam , Gallucci German O.
Published: February 2023

Objective

This study aims to report the implant survival rate of dental implants of partially dentate patients in the anterior mandible and the potential risk indicators for implant failure.

Materials and Methods

Patients with implant‐supported restorations of single or multiple teeth in the anterior mandible restored with fixed partial implant‐supported restorations were evaluated. Patient demographic data, implant placement timing, and loading protocol, biological and/or technical complications at the time of the last clinical and radiographic follow‐up visit were registered. Survival rate, success rate, and potential risk indicators for implant failure were calculated.

Results

A total of 108 patients and 186 implants with a mean follow‐up period of 5.48 years (0.1–11.34 years) were included. The 11.3‐year cumulative survival rate was 90.9%. Immediate implant placement (OR = 2.75) (p = .08) and immediate implant loading (OR = 8.8) (p = .02*) indicated a higher risk of failure than late implant placement or loading. When combining both categories (type 1A), an OR = 10.59 (p = .04*) for implant failure was found compared to category 4C. Implants placed following static—computer‐assisted implant surgery (S‐CAIS) showed less risk of failure compared to freehand implant placement (OR = 0.18; 95% CI: 0.02–1.37) (p = .09).

Conclusions

The survival rate of implants placed in the anterior mandible was considerably low (90.9%). S‐CAIS, late placement, and conventional loading are protective factor against implant failure in the anterior mandible.
Shedding a light on the importance of photopatch testing: A 12‐year experience in a dermatology unit
Authors: Codeço Carlos , Alves Pedro Botelho , Figueiredo Ana Carolina , Flor Duarte , Gonçalo Margarida
Published: February 2023

Background

Photopatch testing has been standardized for diagnosing photoallergic contact dermatitis but is still infrequently used.

Objectives

To characterize photopatch test (PPT) results and their clinical relevance.

Methods

We collected retrospective data from patients photopatch tested in our Dermatology Unit (2010–2021), using the European PPT ‘baseline’ series, other allergens, and patient's own products, when appropriate.

Results

Out of 223 patients, 75 patients (33.6%) were reactive with 124 positive PPT reactions, considered relevant in 56/223 patients (25.1%) and in 72/124 reactions (58.1%). Most reactions were caused by topical drugs (n = 33; 45.8%), such as ketoprofen or promethazine, and 7 (9.8%) by systemic drugs, such as hydrochlorothiazide and fenofibrate. ‘Classical’ ultraviolet filters were responsible for six positive PPT reactions whereas there was only three relevant PPT to the ‘newer’ UV filters. Patients' sunscreens/cosmetics or plant extracts caused 10 positive PPT each. Additional patch test reactions were observed, mostly to Tinosorb® M.

Conclusion

Contrary to the trend in ACD, most positive PPT reactions were caused by topical drugs, outweighing ultraviolet filters and cosmetics. We stress the low reactivity to the ‘newer’ UV filters included in the PPT series. PPT was occasionally positive in systemic drug photosensitivity, but overall PPT reactivity was low.