bluuebunny/crossref_metadata_2025 huggingface dataset:
387 Minimally Invasive TTC Arthrodesis - Novel Arthroscopic Assisted Hindfoot Nailing
Authors: Lingnau L , Morris R , Cheruvu MS , Mumtaz H
Published: November 2022

Aim

Tibiotalocalcaneal arthrodesis is a salvage procedure for advanced primary degenerative joint disease of the hindfoot and ankle, failed primary fixation, post-traumatic osteoarthritis, or Charcot disease. Hindfoot nailing has been associated with complications in up to 40% of cases. There is limited literature on arthroscopic arthrodesis, as an advanced and minimally invasive technique.

Our aim is to evaluate this pioneering minimally invasive procedure in terms of radiological and operative outcomes.

Method

We conducted a retrospective analysis of all patients who underwent this procedure at a single centre by a specialist foot and ankle service. We noted procedure indication, post-operative complications, and post-operative outcome in all patients. Outcomes include wound defects or infection, radiographic evidence of fusion, fixation failure, venous thromboembolism (VTE), and reoperation.

Results

A total of 12 patients underwent surgery with an average age of 75± 22 years. Indication for surgery included: 2 patients requiring fusion for severe primary osteoarthritis, 3 patients underwent primary arthrodesis following trauma and 7 patients underwent arthrodesis as a salvage procedure following failed primary fracture management.

No patients had post-operative wound complications that required re-admission or a return to theatre, no VTE events, no fixation failures and 1 removal of screw for prominence. 6 patients have clinical and radiographic evidence of fusion, with the remaining 6 patients still under active follow-up and all still within 4 months of their fusion surgery.

Conclusions

Our current experience suggests that arthrodesis is achievable with this novel minimally invasive approach, which is a safe and reproducible procedure without increase in operative complications.
905 Improving Confidence in Plastering Across Specialties: A Hands-on Approach
Authors: Sambhwani S , Baba M , Hirschowitz D , Shrestha S , Khairandish H
Published: November 2022

Aim

Plaster of Paris casts form one the most basic yet effective treatment for acute orthopaedic fractures and often form a permanent treatment methodology. Patients with fractures present at all times of the day to acute services and require prompt stabilisation. Casts however do present some risks including compartment syndrome and skin ulcerations. Our quality improvement aimed to improve confidence in healthcare providers across different specialities in managing plasters.

Method

Focussed workshops conducted by expert plaster technicians under the supervision of an experienced orthopaedic consultant were conducted for upper and lower limb injuries. Additional workshops encompassing plaster safety and other trauma splints were delivered. Candidates ranged across different grades and included nurse practitioners and qualified doctors.

Confidence scores (out of five) measured on a Likert scale were obtained from 25 participants.

Results

Knowledge about plasters including type of plaster matched to injury improved from a mean score of 3 to 4.5. Confidence in applying upper limb plasters improved from a mean score 3 to 4.7 and applying lower limb plasters improved from a mean score of 3.25 to 4.8. Confidence in plaster safety including acute conditions and safe removal improved from a mean score of 2 to 4.6. Confidence in applying acute splints improved from a mean score of 1.5 to 4.3.

Conclusions

Our quality improvement project improve the confidence in practitioners managing acute orthopaedic patients with an emphasis on plaster safety and acute splints. It has been formally adopted on a regular basis as a teaching program.
948 Traumatic Native Hip Dislocation Without Associated Fracture: A Case Series of 13 Patients Over 9 Years
Authors: Varma J , Jones C , Fowler T , Chesser T , Ward A , Acharya M
Published: November 2022

Aim

Traumatic native hip dislocation (NHD) is rarely without an associated fracture or due to low energy trauma. Posterior dislocation is the most common pattern of hip dislocation. In most cases, closed reduction is successful, but occasionally open reduction is required to achieve appropriate reduction. The aim of our study was to present the 9-year experience from our institution of this rare injury pattern and to comment on how our experience correlates with the current literature.

Method

This is a retrospective case series of all adult patients (> 16 years old) with a traumatic NHD without fracture presented and/or treated at our institution, between the 1st of January 2012 and 22nd June 2021.

Results

Thirteen cases of traumatic NHD were identified (38.4% female). The mean age was 26.5 years. Typically, younger patients were involved in lower energy injuries. The direction of hip dislocation was posterior in 10 cases. Associated injuries were seen in 3 patients. 12 cases underwent successful closed reduction, and 1 case was operatively managed. 3 cases had a previous hip pathology including femoroacetabular impingement, cam lesion and childhood slipped upper femoral epiphysis.

Conclusions

Traumatic NHD without associated fracture is a rare injury pattern, most commonly occurring in patients under the age of thirty. A target of 6 hours for reduction should be employed as this will reduce the risk of AVN in those who have not permanently damaged the vessels at the time of injury.
157 Stent Encrustation and Indwelling Stent Times
Authors: Debo-Aina A , Datta S , Rix G , Keoghane S , Maan Z
Published: November 2022

Introduction

A pathways streamlining stone management identified four rate-limiting processes causing delay and affecting outcome. Key performance indicators (KPI) with set targets were created to address them. These are:

Ureteric-stents cause morbidity if left in-situ long-term. This includes bacterial colonization and encrustation.

Methods:

Aim

a) identify IDST during pre-COVID and COVID periods, b) review encrusted-stents removed within the study timeframe and c) root-cause for delayed stent removal and encrustation.

Stent register reviewed between Jan-2019 and Mar-2021. Mean IDST pre- and post-COVID calculated. Information on indication, insertion date and removal retrieved from register and clinical-notes. Root-cause analysis to identify factors influencing delayed removal and encrustation.

Results

841 stents inserted within study timeline; 436 pre-COVID and 405 during COVID. Identical stent-times for both periods, 86% cases pre-COVID and 85% during COVID having IDST <12 weeks. Average IDST of 6 weeks and 5 weeks in pre-COVID and COVID periods respectively. 11 encrusted-stents removed (7 pre-COVID, and 4 COVID), with average encrusted-stent duration of 29 weeks pre-COVID and 16 weeks during COVID. Factors involved in encrustation and delayed removal include systems and patient-related factors, failed initial removal, complex surgical planning, ESWL and dissolution therapy.

Discussion & Conclusions

No difference in IDST during pre-COVID and COVID periods. A lowered encrusted IDST during COVID, likely attributed to departmental prioritisation of stone-pathway, stent register, and use of a green-listed operative site.
488 TULA for Bladder Tumours in a University Teaching Hospital: Outcomes Over a 2-Year Period
Authors: Harrison N , Bashir J
Published: November 2022

Aim

TULA (Transurethral laser ablation) of bladder tumours is a relatively non-invasive procedure that is carried out on a day-case basis under local anaesthesia, providing an attractive option for treating recurrent non-muscle invasive bladder cancer (NMIBC). However, data describing efficacy rates are limited.

Method

We carried out a retrospective audit of all TULA procedures carried out for bladder lesions between January 2018 and December 2019. Patients were identified using clinical coding and data collected using electronic case note data. Analysis was performed using Microsoft Excel.

Results

48 patients were identified, 75% were male and the average age was 77. Performance status (PS) was formally documented in 6 patients, with a median of 2.5. A total of 77 TULA procedures were identified. 7 patients had TULA as primary treatment, all but one of these patients had significant co-morbidities.

Biopsies were taken in 83% of procedures. Recurrence rate at 3 months was 29% (n=14). 18% (n=8) of patients went on to have repeat TULA and the remainder went on to have TURBT or biopsy and cystodiathermy. Of those patients with recurrence, 18% had disease progression. 1 patient required catheterisation and irrigation overnight, all other patients were discharged the same day. No patients required re-admission.

Conclusions

TULA is a safe, well tolerated procedure to treat low-grade, recurrent bladder tumours. It can also be used as a palliative procedure for high-grade lesions in patients with multiple co-morbidities. Future work includes collection of objective data on tolerance in the form of VAS pain scoring.
361 Carotid Endarterectomy Pathway at a Hub Site – the Impact of COVID-19
Authors: Alawattegama LH , Siddiqui M
Published: November 2022

Aim

NICE Guidelines recommend that all patients who suffer from a TIA or non-disabling stroke are rapidly assessed and imaged. Patients suspected of having symptomatic carotid stenosis should be referred to a Vascular Centre for consideration of urgent carotid endarterectomy (CEA) within two weeks.

Our aim was to assess the current referral-to-treatment timeline for carotid surgery in our Vascular Centre against these standards and explore the impact of the COVID-19 Pandemic on this.

Method

We retrospectively interrogated the National Vascular Registry to identify patients undergoing CEA “pre-pandemic” (Jan – Dec 2019) and in a “contemporary period” (Jan – Sept 2021)

Results

A total of 129 patients underwent CEA in the defined periods, including pre-Pandemic (80 patients) and contemporary (49 patients) periods. One patient had to be excluded due to inability to identify date of first symptoms.

2019 Data: The times (median) from symptoms to surgery were 10 days (interquartile range (IQR) 23 days), from imaging-to-referral, one day and from vascular review to surgery, two days.

2021 Data: The times (median) from symptoms to surgery were 10 days (IQR 12 days), from imaging-to-referral, two days and from vascular review to surgery, one day.

Conclusions

The median time from symptoms to surgery has remained the same from pre-Pandemic data, though there is a decrease in IQR in current practice. We recommend creating a CEA Pathway to optimise the carotid service.
528 A Single-Centre Retrospective Study in a Large Tertiary Renal Centre on the Management of Infected Arteriovenous Grafts
Authors: Chow BJ , Chowdary P , Khurram M A , Mohamed IH
Published: November 2022

Aim

Prosthetic arteriovenous grafts (AVGs) are often used as tertiary vascular access for haemodialysis in patients with exhausted autogenous options. AVGs are associated with an increased risk of infection which can lead to excess morbidity and life-threatening complications. Infected AVGs are challenging to manage, and the current evidence remains unclear on optimal strategy with arguments for conservative management, salvaging with revision or surgical excision (subtotal or total). This study sought to evaluate the management of infected AVGs by examining the clinical outcomes of patients with infected AVGs managed in our institution.

Method

We conducted a single-centre retrospective study of all AVG infections managed (conservative management via antibiotics; graft revision; surgical excision) in a large tertiary renal centre between June 2016 to May 2021. Primary outcome was mortality at 1 year. Secondary outcome was functional vascular access at 6 months and 1 year. Data were extracted from electronic patient records, radiology imaging and reporting.

Results

34 patients were included in our study (14.7% conservatively managed; 14.7% revision; 70.6% surgical excision) with a mean age of 60.4 ± 14.4 years (67.6% males). Average time from AVG placement to presentation was 11.8 months. 1 year mortality was 14.7%. Functional vascular access at 6 months in the three groups was 60%, 60% and 10% and 1-year functional vascular access was 60%, 75% and 42% respectively.

Conclusion

Surgically excised infected AVGs are associated with poor 6-month and 1-year vascular access outcomes. The findings suggest that conservative management and/or revision are more prudent given their higher probability of subsequent functional access.
586 Case Series: Neurostimulation - a Promising Option for Treatment of Chronic Peripheral Arterial Disease When Revascularization and Conservative Management Are Unsuitable
Authors: Singhania A , Quddus A
Published: November 2022

Parasympathetic stimulation has been implicated in improving circulation in the extremities by causing arteriolar dilatation, which could plausibly be useful in patients with peripheral arterial disease (PAD).

Herein, we illustrate 5 cases (4 males and 1 female, age 40–75) of chronic disabling intermittent limb claudication without any ischaemic rest pain who were offered Neurostimulation since conservative treatment did not help and no other revascularization options were deemed suitable.

Each of these patients had a pre-neurostimulation arterial duplex scan to depict the extent of occlusion; measure diameter of vessels and their blood flow, ABPI and absolute ankle pressure. Pain score, claudication distance and impact on quality-of-life pre-stimulation were recorded in the patient clinic notes. Non-invasive Ducest Neurostimulator was implanted in the auricular fossa triangularis for two sessions of 3 weeks treatment. Post-neurostimulation arterial duplex scan was repeated to compare any changes in the vessel diameter, blood flow and ABPI.

Significant improvement in the symptoms of PAD was noted in all the cases. Post-treatment, the patients felt much more comfortable- their pain score reduced significantly (to 0 in 2 of the cases); and 2 to 16-fold increase in their walking distance as compared to pre-treatment. Remarkable symptomatic relief was in line with profound (2–8 times) improvement in blood flow which was quantified using vessel diameter, tibial flow volume, and hand-held doppler signal. ABPI and absolute pressure either remained near unchanged or increased post treatment.

This series strongly suggests a beneficial role of neurostimulation in the symptomatic treatment of PAD in selective cases.
938 Opportunity Knocks - Reducing Cardiovascular Risk in Patients Undergoing AAA Surveillance
Authors: Evans E , Turner J , Meldrum A
Published: November 2022

Aim

Secondary prevention medication is recognised to reduce cardiovascular events in patients with established atherosclerotic disease; in the form of antiplatelet and lipid-lowering therapy. Yet a lack of consensus between the European Society of Vascular Surgery (ESVS) (Wanhainen et al., 2019) and NICE guidelines (NICE, 2021b; a) is recognised (Saratzis et al., 2017). Abdominal aortic aneurysm (AAA) is a manifestation of peripheral arterial disease, and medical optimisation should be considered for those diagnosed (Wanhainen et al., 2019; NICE, 2021b). Compliance of secondary prevention in this patient group was assessed in our unit which serves over 1.4 million patients across the West of Scotland. The secondary aim was to optimise those identified.

Method

Data was collected systematically, analysed, and results held to the standard set by ESVS, NICE and current literature. Current medication information was obtained through Community Pharmacy Scotland.

Results

Out of 632 patients, 74.1% were on an antiplatelet, 75.6% on a statin, and 64.7% on both. 71.2% of these patients were male, mean age was 73.9 years. Circumstances that outweigh the introduction of such medications were explored, and changes have been recommended to patients and general practitioners where appropriate. Preliminary data on second cycle shows increased uptake in the recommended medications.

Conclusions

Studies have shown significantly improved survival rates for AAA patients with prescribed secondary prevention therapy (Bahia et al.,2016; Cheng et al.,2019). This study has identified 32.8% whose cardiovascular health can be optimised, and realised through liaison with general practitioners, thus protecting these patients from adverse cardiovascular outcome and death.
Medical Student Debt and the US Infectious Diseases Workforce
Authors: Mohareb Amir M , Brown Tyler S
Published: November 2022

Student debt in the United States is at historically high levels and poses an excessive burden on medical graduates. Studies suggest that financial limitations dissuade some medical trainees from pursuing careers in infectious diseases (ID) and other cognitive specialties, despite their interest in the subject matter. Addressing student debt may have a transformative impact on ID recruitment, diversification of the ID workforce, and contributions of ID physicians to underserved public health needs. Relief of student debt also has the potential to narrow the racial wealth gap because nonwhite students are more likely to finance their postsecondary education, including medical school, with student loans, yet they have a lower earning potential following graduation. An executive order from the Biden-Harris administration announced in August 2022 presents a first step toward student debt relief, but the policy would need to be expanded in volume and scope to effectively achieve these goals.
“Care for Me, Too”: A Novel Framework for Improved Communication and Support Between Dementia Caregivers and the Home Health Care Team
Authors: Burgdorf Julia G , Reckrey Jennifer , Russell David
Published: November 2022

Background and Objectives

Identifying and meeting the needs of family and unpaid caregivers (hereafter, “caregivers”) during home health (HH) can improve outcomes for patients with Alzheimer’s Disease and Related Dementias (ADRD). However, little is known regarding ADRD caregivers’ perspectives on communication and support from the HH care team. The study objectives were to identify ADRD caregivers’ common support needs during HH and preferences for addressing these needs, to inform future development of an assessment and support intervention.

Research Design and Methods

We conducted semistructured key informant interviews with caregivers who had recently assisted a HH patient with ADRD (n = 27). Interview transcripts were analyzed using directed content analysis.

Results

Caregivers identified four major support needs: assistance navigating insurance and service coverage, training on nursing tasks, referral to respite care, and information regarding ADRD disease progression. Caregivers described major barriers to communicating these needs, including never being directly asked about their needs and information discontinuity within the HH care team. Incorporating caregiver recommendations, we propose a new model of assessment and support in which the HH care team (a) proactively asks about caregiver needs, (b) presents available supportive resources, (c) solicits information regarding the patient’s needs and routine, and (d) stores and shares this information within the medical record.

Discussion and Implications

Findings reveal critical gaps in current patterns of support for ADRD caregivers during HH and suggest directions for an assessment and support intervention that explicitly queries caregivers on their capacity and needs, with content tailored to the HH setting.
Viral Kinetics in Sylvatic Yellow Fever Cases
Authors: Avelino-Silva Vivian I , Thomazella Mateus Vailant , Marmorato Mariana Prado , Correia Carolina A , Dias Juliana Z C , Maestri Alvino , Cerqueira Natalia B , Moreira Carlos H V , Buccheri Renata , Félix Alvina C , Zanella Luiz G F A B E , Costa Priscilla R , Kallás Esper G
Published: November 2022

Background

Yellow fever is a mosquito-borne zoonotic disease caused by yellow fever virus (YFV). Between 2017 and 2019, more than 504 human cases and 176 deaths were confirmed in the outskirts of São Paulo city. Throughout this outbreak, studies suggested a potential association between YFV viremia and mortality.

Methods

Viral ribonucleic acid was measured using reverse-transcription quantitative polymerase chain reaction in plasma samples collected at up to 5 time points, between 3 and 120 days after symptoms onset.

Results

Eighty-four patients with confirmed YFV infection were included. Most were males, median age was 42, and 30 (36%) died. Deceased patients were older than survivors (P = .003) and had a higher viremia across all time points (P = .0006). Mean values of viremia had a positive, statistically significant correlation with peak values of neutrophils, indirect bilirubin, aspartate transaminase, international normalized ratio, and creatinine. Finally, a Cox proportional hazards model adjusted for age and laboratory variables showed that viremia is independently associated with death, with a mean 1.84-fold increase (84%) in the hazard of death (P < .001) for each unit increase in mean log10 viremia.

Conclusions

Our results raise the importance of monitoring YFV viremia and suggest a potential benefit of antiviral drugs or neutralizing monoclonal antibodies early in the course of this infection to improve disease outcomes.
Portal venous gas accompanied by gallbladder torsion: a case report
Authors: Tohma Takayuki , Kobe Yoshiro , Yoshida Mitsuhiko , Ushio Masaya
Published: November 2022

Portal venous gas (PVG) generally suggests critically ill conditions such as severe bowel ischemia. We herein report a rare case of gallbladder torsion with PVG. An 88-year-old woman complained of right hypogastric pain. Ultrasonography (US) showed diffuse wall thickening of her gallbladder and mobile echogenic foci moving inside the portal venous branches. Computed tomography showed a thickened wall of the gallbladder with poor enhancement and tiny pockets of air in the portal venous branches (segments 4 and 5). There was no evidence of other visceral ischemia. She was diagnosed with necrotic cholecystitis and immediately underwent an emergency operation. We found a gangrenous gallbladder with 180° clockwise rotation along the longitudinal axis and performed cholecystectomy. We confirmed the disappearance of PVG with US after the operation. Her postoperative course was uneventful. Gallbladder diseases can produce PVG, and US might be a useful diagnostic modality to evaluate changes in PVG.
Virulence is one of the mechanisms of vulvovaginal candidiasis recurrence, rather than drug resistance
Authors: Li Xinzheng , Chen Shi , Lyu Xiangcai , Tian Jiyun
Published: November 2022

To explore the mechanism of vulvovaginal candidiasis (VVC) recurrence. A total of 127 strains of Candida albicans (C. albicans) were collected, including 58, 40, and 29 strains from the recurrent vulvovaginal candidiasis (RVVC), VVC, and asymptomatic carrier (AC), respectively. The strains’ virulence such as in vivo hypha formation rate, germ tube formation rate, biofilm formation ability, and sensitivity to five common antifungals were detected. The in vivo hypha formation rates of C. albicans from the RVVC (55.2%) and VVC (40.0%) were significantly higher than that from the AC (0%) (P < .001). The median germ tube formation rate of the RVVC was 88.2%, which was higher than that of the VVC and AC (59.9% and 65.6%), respectively (P < .001). The median absorbance of the biofilm formation test for strains in the RVVC was 0.380, considerably higher than that in the VVC and AC (0.246 and 0.254) (P < .001). The drug sensitivity rate of the strains to 5-fluorocytosine and itraconazole and the ratio of strains sensitive to all the five antifungals in the VVC group were lower than those in the RVVC and AC groups. In conclusion, the virulence of strains from the RVVC is stronger than that of strains from the VVC and AC, the antifungal resistance rate of strains from the RVVC group is lower than that of strains from the VVC group. So, it is suitable to argue that the strains’ virulence is one of the mechanisms for the relapse of RVVC, rather than its antifungal resistance.
Star formation time-scale in the molecular filament WB 673
Authors: Ryabukhina O L , Kirsanova M S , Henkel C , Wiebe D S
Published: November 2022

We present the observations of ammonia emission lines toward the interstellar filament WB 673 hosting the dense clumps WB 673, WB 668, S233-IR, and G173.57+2.43. LTE analysis of the lines allows us to estimate gas kinetic temperature (≲30K in all the clumps), number density (7–17 × 103 cm−3), and ammonia column density (≈1–1.5 × 1015 cm−2) in the dense clumps. We find signatures of collapse in WB 673 and presence of compact spatially unresolved dense clumps in S233-IR. We reconstruct 1D density and temperature distributions in the clumps and estimate their ages using astrochemical modelling. Considering CO, CS, NH3, and N2H+ molecules (plus HCN and HNC for WB 673), we find a chemical age of tchem = 1–3 × 105 yrs, providing the best agreement between the simulated and observed column densities in all the clumps. Therefore, we consider tchem as the chemical age of the entire filament. A long preceding low-density stage of gas accumulation in the astrochemical model would break the agreement between the simulated and observed column densities. We suggest that rapid star formation over a ∼105 yrs time-scale take place in the filament.
A systematic comparison of galaxy cluster temperatures measured with NuSTAR and Chandra
Authors: Wallbank A N , Maughan B J , Gastaldello F , Potter C , Wik D R
Published: November 2022

Temperature measurements of galaxy clusters are used to determine their masses, which in turn are used to determine cosmological parameters. However, systematic differences between the temperatures measured by different telescopes imply a significant source of systematic uncertainty on such mass estimates. We perform the first systematic comparison between cluster temperatures measured with Chandra and NuSTAR. This provides a useful contribution to the effort of cross-calibrating cluster temperatures due to the harder response of NuSTAR compared with most other observatories. We measure average temperatures for eight clusters observed with NuSTAR and Chandra. We fit the NuSTAR spectra in a hard (3–10 keV) energy band, and the Chandra spectra in both the hard and a broad (0.6–9 keV) band. We fit a power-law cross-calibration model to the resulting temperatures. At a Chandra temperature of 10 keV, the average NuSTAR temperature was $(10.5\pm 3.7)$ and $(15.7\pm 4.6){{\ \rm per\ cent}}$, lower than Chandra for the broad- and hard-band fits, respectively. We explored the impact of systematics from background modelling and multiphase temperature structure of the clusters, and found that these did not affect our results. Our sample are primarily merging clusters with complex thermal structures so are not ideal calibration targets. However, given the harder response of NuSTAR, it would be expected to measure a higher average temperature than Chandra for a non-isothermal cluster, so we interpret our measurement as a lower limit on the difference in temperatures between NuSTAR and Chandra.
Iterative mean-field approach to the spherical collapse of dark matter haloes
Authors: Shi Xun
Published: November 2022

Gravitational collapse of dark matter overdensities leads to the formation of dark matter haloes which embed galaxies and galaxy clusters. An intriguing feature of dark matter haloes is that their density profiles closely follow a universal form irrespective of the initial condition or the corresponding growth history. This represents a class of dynamical systems with emergent universalities. We propose an ‘iterative mean-field approach’ to compute the solutions of the gravitational collapse dynamics. This approach iteratively searches for the evolution of the interaction field ϕ(t) – in this case the enclosed mass profile M(r, t) – that is consistent with the dynamics, thus that ϕ(t) is the fix-point of the iterative mapping, $\mathcal {H}(\phi) = \phi$. The formalism replaces the N-body interactions with one-body interactions with the coarse-grained interaction field, and thus shares the spirit of the mean-field theory in statistical physics. This ‘iterative mean-field approach’ combines the versatility of numerical simulations and the comprehensiveness of analytical solutions, and is particularly powerful in searching for and understanding intermediate asymptotic states in a wide range of dynamical systems where the solutions can not be obtained through the traditional self-similar analysis.
The buildup of galaxies and their spheroids: The contributions of mergers, disc instabilities, and star formation
Authors: Huško Filip , Lacey Cedric G , Baugh Carlton M
Published: November 2022

We use the GALFORM semi-analytical model of galaxy formation and the Planck-Millennium simulation to investigate the origins of stellar mass in galaxies and their spheroids. We compare the importance of mergers and disc instabilities, as well as the starbursts that they trigger. We find that the fraction of galaxy stellar mass formed ex situ (i.e. through mergers; fex) increases sharply from M* = 1011 M⊙ upwards, reaching 80 per cent at M* = 1011.3 M⊙. The massive end of the fex–M* relation does not evolve with redshift, in disagreement with other models. For low-mass galaxies we find larger ex situ contributions at z = 0 than in other models (7–12 per cent), with a decrease towards higher redshifts. Major mergers contribute roughly half of the ex situ mass, with minor mergers and smooth accretion of satellites both accounting for ≈25 per cent, almost independent of stellar mass and redshift. Mergers dominate in building up high-mass (M*, sph > 1011 M⊙) and low-mass (M*, sph < 108.5 M⊙) spheroids. Disc instabilities and their associated starbursts dominate for intermediate-mass spheroids (108.5 < M*, sph < 1011 M⊙) at z = 0. The mass regime where pseudo-bulges dominate is in agreement with observed pseudo-bulge fractions, but the peak value in the pseudo-bulge fraction predicted by GALFORM is likely too high. Starbursts induced by disc instabilities are the dominant channel for spheroid growth at all redshifts, while merger-induced starbursts are relatively negligible, except at very high redshifts (z > 5).
A PAM-free CRISPR/Cas12a ultra-specific activation mode based on toehold-mediated strand displacement and branch migration
Authors: Wu You , Luo Wang , Weng Zhi , Guo Yongcan , Yu Hongyan , Zhao Rong , Zhang Li , Zhao Jie , Bai Dan , Zhou Xi , Song Lin , Chen Kena , Li Junjie , Yang Yujun , Xie Guoming
Published: November 2022

CRISPR (clustered regularly interspaced short palindromic repeats) technology has achieved great breakthroughs in terms of convenience and sensitivity; it is becoming the most promising molecular tool. However, only two CRISPR activation modes (single and double stranded) are available, and they have specificity and universality bottlenecks that limit the application of CRISPR technology in high-precision molecular recognition. Herein, we proposed a novel CRISPR/Cas12a unrestricted activation mode to greatly improve its performance. The new mode totally eliminates the need for a protospacer adjacent motif and accurately activates Cas12a through toehold-mediated strand displacement and branch migration, which is highly universal and ultra-specific. With this mode, we discriminated all mismatch types and detected the EGFR T790M and L858R mutations in very low abundance. Taken together, our activation mode is deeply incorporated with DNA nanotechnology and extensively broadens the application boundaries of CRISPR technology in biomedical and molecular reaction networks.
Estrogen regulates divergent transcriptional and epigenetic cell states in breast cancer
Authors: Ors Aysegul , Chitsazan Alex Daniel , Doe Aaron Reid , Mulqueen Ryan M , Ak Cigdem , Wen Yahong , Haverlack Syber , Handu Mithila , Naldiga Spandana , Saldivar Joshua C , Mohammed Hisham
Published: November 2022

Breast cancers are known to be driven by the transcription factor estrogen receptor and its ligand estrogen. While the receptor's cis-binding elements are known to vary between tumors, heterogeneity of hormone signaling at a single-cell level is unknown. In this study, we systematically tracked estrogen response across time at a single-cell level in multiple cell line and organoid models. To accurately model these changes, we developed a computational tool (TITAN) that quantifies signaling gradients in single-cell datasets. Using this approach, we found that gene expression response to estrogen is non-uniform, with distinct cell groups expressing divergent transcriptional networks. Pathway analysis suggested the two most distinct signatures are driven separately by ER and FOXM1. We observed that FOXM1 was indeed activated by phosphorylation upon estrogen stimulation and silencing of FOXM1 attenuated the relevant gene signature. Analysis of scRNA-seq data from patient samples confirmed the existence of these divergent cell groups, with the FOXM1 signature predominantly found in ER negative cells. Further, multi-omic single-cell experiments indicated that the different cell groups have distinct chromatin accessibility states. Our results provide a comprehensive insight into ER biology at the single-cell level and potential therapeutic strategies to mitigate resistance to therapy.
The Neuroscience Multi-Omic Archive: a BRAIN Initiative resource for single-cell transcriptomic and epigenomic data from the mammalian brain
Authors: Ament Seth A , Adkins Ricky S , Carter Robert , Chrysostomou Elena , Colantuoni Carlo , Crabtree Jonathan , Creasy Heather H , Degatano Kylee , Felix Victor , Gandt Peter , Garden Gwenn A , Giglio Michelle , Herb Brian R , Khajouei Farzaneh , Kiernan Elizabeth , McCracken Carrie , McDaniel Kennedy , Nadendla Suvarna , Nickel Lance , Olley Dustin , Orvis Joshua , Receveur Joseph P , Schor Mike , Sonthalia Shreyash , Tickle Timothy L , Way Jessica , Hertzano Ronna , Mahurkar Anup A , White Owen R
Published: November 2022

Scalable technologies to sequence the transcriptomes and epigenomes of single cells are transforming our understanding of cell types and cell states. The Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative Cell Census Network (BICCN) is applying these technologies at unprecedented scale to map the cell types in the mammalian brain. In an effort to increase data FAIRness (Findable, Accessible, Interoperable, Reusable), the NIH has established repositories to make data generated by the BICCN and related BRAIN Initiative projects accessible to the broader research community. Here, we describe the Neuroscience Multi-Omic Archive (NeMO Archive; nemoarchive.org), which serves as the primary repository for genomics data from the BRAIN Initiative. Working closely with other BRAIN Initiative researchers, we have organized these data into a continually expanding, curated repository, which contains transcriptomic and epigenomic data from over 50 million brain cells, including single-cell genomic data from all of the major regions of the adult and prenatal human and mouse brains, as well as substantial single-cell genomic data from non-human primates. We make available several tools for accessing these data, including a searchable web portal, a cloud-computing interface for large-scale data processing (implemented on Terra, terra.bio), and a visualization and analysis platform, NeMO Analytics (nemoanalytics.org).
MethBank 4.0: an updated database of DNA methylation across a variety of species
Authors: Zhang Mochen , Zong Wenting , Zou Dong , Wang Guoliang , Zhao Wei , Yang Fei , Wu Song , Zhang Xinran , Guo Xutong , Ma Yingke , Xiong Zhuang , Zhang Zhang , Bao Yiming , Li Rujiao
Published: November 2022

DNA methylation, as the most intensively studied epigenetic mark, regulates gene expression in numerous biological processes including development, aging, and disease. With the rapid accumulation of whole-genome bisulfite sequencing data, integrating, archiving, analyzing, and visualizing those data becomes critical. Since its first publication in 2015, MethBank has been continuously updated to include more DNA methylomes across more diverse species. Here, we present MethBank 4.0 (https://ngdc.cncb.ac.cn/methbank/), which reports an increase of 309% in data volume, with 1449 single-base resolution methylomes of 23 species, covering 236 tissues/cell lines and 15 biological contexts. Value-added information, such as more rigorous quality evaluation, more standardized metadata, and comprehensive downstream annotations have been integrated in the new version. Moreover, expert-curated knowledge modules of featured differentially methylated genes associated with biological contexts and methylation analysis tools have been incorporated as new components of MethBank. In addition, MethBank 4.0 is equipped with a series of new web interfaces to browse, search, and visualize DNA methylation profiles and related information. With all these improvements, we believe the updated MethBank 4.0 will serve as a fundamental resource to provide a wide range of data services for the global research community.
HGD: an integrated homologous gene database across multiple species
Authors: Duan Guangya , Wu Gangao , Chen Xiaoning , Tian Dongmei , Li Zhaohua , Sun Yanling , Du Zhenglin , Hao Lili , Song Shuhui , Gao Yuan , Xiao Jingfa , Zhang Zhang , Bao Yiming , Tang Bixia , Zhao Wenming
Published: November 2022

Homology is fundamental to infer genes’ evolutionary processes and relationships with shared ancestry. Existing homolog gene resources vary in terms of inferring methods, homologous relationship and identifiers, posing inevitable difficulties for choosing and mapping homology results from one to another. Here, we present HGD (Homologous Gene Database, https://ngdc.cncb.ac.cn/hgd), a comprehensive homologs resource integrating multi-species, multi-resources and multi-omics, as a complement to existing resources providing public and one-stop data service. Currently, HGD houses a total of 112 383 644 homologous pairs for 37 species, including 19 animals, 16 plants and 2 microorganisms. Meanwhile, HGD integrates various annotations from public resources, including 16 909 homologs with traits, 276 670 homologs with variants, 398 573 homologs with expression and 536 852 homologs with gene ontology (GO) annotations. HGD provides a wide range of omics gene function annotations to help users gain a deeper understanding of gene function.
CRAMdb: a comprehensive database for composition and roles of microbiome in animals
Authors: Lei Bingbing , Xu Yueren , Lei Yunjiao , Li Cunyuan , Zhou Ping , Wang Limin , Yang Qing , Li Xiaoyue , Li Fulin , Liu Chuyang , Cui Chaowen , Chen Tong , Ni Wei , Hu Shengwei
Published: November 2022

CRAMdb (a database for composition and roles of animal microbiome) is a comprehensive resource of curated and consistently annotated metagenomes for non-human animals. It focuses on the composition and roles of the microbiome in various animal species. The main goal of the CRAMdb is to facilitate the reuse of animal metagenomic data, and enable cross-host and cross-phenotype comparisons. To this end, we consistently annotated microbiomes (including 16S, 18S, ITS and metagenomics sequencing data) of 516 animals from 475 projects spanning 43 phenotype pairs to construct the database that is equipped with 9430 bacteria, 278 archaea, 2216 fungi and 458 viruses. CRAMdb provides two main contents: microbiome composition data, illustrating the landscape of the microbiota (bacteria, archaea, fungi, and viruses) in various animal species, and microbiome association data, revealing the relationships between the microbiota and various phenotypes across different animal species. More importantly, users can quickly compare the composition of the microbiota of interest cross-host or body site and the associated taxa that differ between phenotype pairs cross-host or cross-phenotype. CRAMdb is freely available at (http://www.ehbio.com/CRAMdb).
REBASE: a database for DNA restriction and modification: enzymes, genes and genomes
Authors: Roberts Richard J , Vincze Tamas , Posfai Janos , Macelis Dana
Published: November 2022

REBASE is a comprehensive and extensively curated database of information about the components of restriction-modification (RM) systems. It is fully referenced and provides information about the recognition and cleavage sites for both restriction enzymes and DNA methyltransferases together with their commercial availability, methylation sensitivity, crystal and sequence data. All completely sequenced genomes and select shotgun sequences are analyzed for RM system components. When PacBio sequence data is available, the recognition sequences of many DNA methyltransferases (MTases) can be determined. This has led to an explosive growth in the number of well-characterized MTases in REBASE. The contents of REBASE may be browsed from the web rebase.neb.com and selected compilations can be downloaded by FTP (ftp.neb.com). Monthly updates are also available via email.
SulfAtlas, the sulfatase database: state of the art and new developments
Authors: Stam Mark , Lelièvre Pernelle , Hoebeke Mark , Corre Erwan , Barbeyron Tristan , Michel Gurvan
Published: November 2022

SulfAtlas (https://sulfatlas.sb-roscoff.fr/) is a knowledge-based resource dedicated to a sequence-based classification of sulfatases. Currently four sulfatase families exist (S1–S4) and the largest family (S1, formylglycine-dependent sulfatases) is divided into subfamilies by a phylogenetic approach, each subfamily corresponding to either a single characterized specificity (or few specificities in some cases) or to unknown substrates. Sequences are linked to their biochemical and structural information according to an expert scrutiny of the available literature. Database browsing was initially made possible both through a keyword search engine and a specific sequence similarity (BLAST) server. In this article, we will briefly summarize the experimental progresses in the sulfatase field in the last 6 years. To improve and speed up the (sub)family assignment of sulfatases in (meta)genomic data, we have developed a new, freely-accessible search engine using Hidden Markov model (HMM) for each (sub)family. This new tool (SulfAtlas HMM) is also a key part of the internal pipeline used to regularly update the database. SulfAtlas resource has indeed significantly grown since its creation in 2016, from 4550 sequences to 162 430 sequences in August 2022.
A systematic review and meta-analysis of the effect of intravitreal VEGF inhibitors on cardiorenal outcomes
Authors: Lees Jennifer S , Dobbin Stephen J H , Elyan Benjamin M P , Gilmour David F , Tomlinson Laurie P , Lang Ninian N , Mark Patrick B
Published: November 2022

Background

Vascular endothelial growth factor inhibitors (VEGFis) have transformed the treatment of many retinal diseases, including diabetic maculopathy. Increasing evidence supports systemic absorption of intravitreal VEGFi and development of significant cardiorenal side effects.

Methods

We conducted a systematic review and meta-analysis (PROSPERO: CRD42020189037) of randomised controlled trials of intravitreal VEGFi treatments (bevacizumab, ranibizumab and aflibercept) for any eye disease. Outcomes of interest were cardiorenal side effects (hypertension, proteinuria, kidney function decline and heart failure). Fixed effects meta-analyses were conducted where possible.

Results

There were 78 trials (81 comparisons; 13 175 participants) that met the criteria for inclusion: 47% were trials in diabetic eye disease. Hypertension (29 trials; 8570 participants) was equally common in VEGFi and control groups {7.3 versus 5.4%; relative risk [RR] 1.08 [95% confidence interval (CI) 0.91–1.28]}. New or worsening heart failure (10 trials; 3384 participants) had a similar incidence in VEGFi and control groups [RR 1.03 (95% CI 0.70–1.51)]. Proteinuria (5 trials; 1902 participants) was detectable in some VEGFi-treated participants (0.2%) but not controls [0.0%; RR 4.43 (95% CI 0.49–40.0)]. Kidney function decline (9 trials; 3471 participants) was similar in VEGFi and control groups. In participants with diabetic eye disease, the risk of all-cause mortality was higher in VEGFi-treated participants [RR 1.62 (95% CI 1.04–2.46)].

Conclusion

In trials of intravitreal VEGFi, we did not identify an increased risk of cardiorenal outcomes, although these outcomes were reported in only a minority of cases. There was an increased risk of death in VEGFi-treated participants with diabetic eye disease. Additional scrutiny of post-licensing observational data may improve the recognition of safety concerns in VEGFi-treated patients.
Squeezing microwaves by magnetostriction
Authors: Li Jie , Wang Yi-Pu , You Jian-Qiang , Zhu Shi-Yao
Published: November 2022

Squeezed light finds many important applications in quantum information science and quantum metrology, and has been produced in a variety of physical systems involving optical non-linear processes. Here, we show how a non-linear magnetostrictive interaction in a ferrimagnet in cavity magnomechanics can be used to reduce quantum noise of the electromagnetic field. We show optimal parameter regimes where a substantial and stationary squeezing of the microwave output field can be achieved. Realization of the scheme is within reach of current technology in cavity electromagnonics and magnomechanics. Our work provides a new and practicable approach for producing squeezed vacuum states of electromagnetic fields, and may find promising applications in quantum information processing and quantum metrology.
Effect of Common ER Stress–Inducing Drugs on the Growth and Lipid Phenotypes of Chlamydomonas and Arabidopsis
Authors: Je Sujeong , Lee Yuree , Yamaoka Yasuyo
Published: November 2022

Endoplasmic reticulum (ER) stress is caused by the stress-induced accumulation of unfolded proteins in the ER. Several compounds are used to induce the unfolded protein response (UPR) in animals, with different modes of action, but which ER stress–inducing drugs induce ER stress in microalgae or land plants is unclear. In this study, we examined the effects of seven chemicals that were reported to induce ER stress in animals on the growth, UPR gene expression and fatty acid profiles of Chlamydomonas reinhardtii (Chlamydomonas) and Arabidopsis thaliana (Arabidopsis): 2-deoxyglucose, dithiothreitol (DTT), tunicamycin (TM), thapsigargin, brefeldin A (BFA), monensin (MON) and eeyarestatin I. In both model photosynthetic organisms, DTT, TM, BFA and MON treatment induced ER stress, as indicated by the induction of spliced bZIP1 and bZIP60, respectively. In Chlamydomonas, DTT, TM and BFA treatment induced the production of transcripts related to lipid biosynthesis, but MON treatment did not. In Arabidopsis, DTT, TM, BFA and MON inhibited seed germination and seedling growth with the activation of bZIP60. These findings lay the foundation for using four types of ER stress–inducing drugs in photosynthetic organisms, and they help uncover the mode of action of each compound.