bluuebunny/crossref_metadata_2025 huggingface dataset:
Acute gastric conduit dilation after minimally invasive esophagectomy: a 10-year experience
Authors: Takahashi Hideo , Peng June , Brady Maureen , Roche Charles , Catalfamo Kayla , Attwood Kristopher , Yendamuri Sai , Demmy Todd L , Hochwald Steven N , Kukar Moshim
Published: June 2022

Despite decreasing overall morbidity with minimally invasive esophagectomy (MIE), conduit functional outcomes related to delayed emptying remain challenging, especially in the immediate postoperative setting. Yet, this problem has not been described well in the literature. Utilizing a single institutional prospective database, 254 patients who underwent MIEs between 2012 and 2020 were identified. Gastric conduit dilation was defined as a conduit occupying >40% of the hemithorax on the postoperative chest X-ray. Sixty-seven patients (26.4%) demonstrated acute conduit dilation. There was a higher incidence of conduit dilation in the patients who underwent Ivor Lewis esophagectomy compared to those with a neck anastomosis (67.2% vs. 47.1%; P = 0.03). Patients with dilated conduits required more esophagogastroduodenoscopies (EGD) (P < 0.001), conduit-related reoperations within 180 days (P < 0.001), and 90-day readmissions (P = 0.01). Furthermore, in 37 patients (25.5%) undergoing Ivor Lewis esophagectomy, we returned to the abdomen after intrathoracic anastomosis to reduce redundant conduit and pexy the conduit to the crura. While conduit dilation rates were similar, those who had intraabdominal gastropexy required EGD significantly less and trended toward a lower incidence of conduit-related reoperations (5.6% vs. 2.7%). Multivariable analysis also demonstrated that conduit dilation was an independent predictor for delayed gastric conduit emptying symptoms, EGD within 90 days, conduit-related reoperation within 180 days, and 30-day as well as 90-day readmission. Patients undergoing MIE with acute gastric conduit dilation require more endoscopic interventions and reoperations.
Patients’ acceptance of less blood pressure measurement in consultation: a cross-sectional study in general practice
Authors: Richard Amélie , Trefond Jeromine , Lambert Céline , Balandreaud Guillaume , Vaillant-Roussel Hélène
Published: June 2022

Purpose

Blood pressure (BP) is measured at almost every general practitioner (GP) consultation in the region of Auvergne, France. A 2018 qualitative study shows that GPs measure BP to satisfy patients, whereas patients declare themselves indifferent to the absence of the measurement. The objective was to validate the results of a qualitative study, to quantitatively assess patient satisfaction when BP is not measured, and to study the factors associated with the degree of patient satisfaction.

Methods

This was a quantitative observational study conducted using self-questionnaires among patients in medical practices in Auvergne.

Results

Four hundred and ninety-two questionnaires were evaluated in 20 medical practices. Sixty percent of patients had indifferent or favorable feelings in the absence of BP measurement. In bivariate analysis, young age, male sex, absence of pathology, and low frequency of visits were associated with indifferent or favorable feelings in the absence of BP measurement. In multivariable analysis, a history of hypertension and psychiatric history were associated with unfavorable feelings. The intraclass correlation coefficient for practice-related variability was 5.6%. Patients’ susceptibility to having particularly favorable or unfavorable feelings could be related to their GP (physician effect).

Conclusion

The hypothesis put forward in the qualitative study is confirmed: the majority of patients are in favor of or indifferent to the absence of BP measurement in general practice. General practice could be more efficient by measuring BP less frequently and better.
Kinetic effects on the 660-km-phase transition in mantle upstreams and seismological implications
Authors: Lessing Stephan , Dobson David P , Rost Sebastian , Cobden Laura , Thomas Christine
Published: June 2022

The effects of reaction kinetics of bridgmanite and ferropericlase transforming to ringwoodite on elastic properties in upwelling mantle are investigated using data of kinetic experiments and internally self-consistent thermodynamic modelling of density and seismic velocities. The kinetic experiments show inhibited grain growth of ringwoodite. At the initiation of ringwoodite growth, bridgmanite completely transforms to a metastable pyrope-bearing garnet. Ringwoodite then gradually grows from the metastable assemblage of ferropericlase and garnet. The changes in mineralogy result in a low-velocity zone directly above the 660 km seismic discontinuity due to the lower seismic velocities and densities of ferropericlase and garnet compared to ringwoodite and bridgmanite. The modelling of the effects of reaction kinetics and its effect on seismic structure at ∼660 km depth shows more sensitivity to grain size than to temperature and upwelling rate. Modelling 1-D synthetic seismograms of PP (SS) underside reflections off the kinetically inhibited backward reaction to ringwoodite shows advanced traveltimes of underside reflections off ∼660 km depth of 0.2–0.8 s (1.2–1.6 s) for upwelling rates of 50 cm yr–1 and initial grain sizes between 5 and 20 cm due to the low-velocity zone above the 660 km discontinuity. The finite width of the low-velocity layer results in frequency-dependent behaviour of PP and SS underside reflection amplitudes, with higher amplitudes towards shorter periods. The effect on the traveltimes of P-to-s conversions used for receiver function is small (<0.7 s) but the inhibited backward reaction leads to strong amplitude changes and significant waveform variations. The effects of reaction kinetics in mantle upwellings might serve as an additional means to map regions of large-scale upwellings and to constrain grain size in the lower mantle.
Quantifying microseismic noise generation from coastal reflection of gravity waves recorded by seafloor DAS
Authors: Guerin G , Rivet D , van den Ende M P A , Stutzmann E , Sladen A , Ampuero J-P
Published: June 2022

Secondary microseisms are the most energetic noise in continuous seismometer recordings. They are generated by interactions between ocean waves, including between gravity waves incident on and reflected from the coast. Coastal reflections of ocean waves leading to coastal microseismic sources are hard to estimate in various global numerical wave models, and independent quantification of these coastal sources through direct measurements can greatly improve these models. Here, we exploit a 41-km-long submarine optical fibre (OF) cable located offshore Toulon, France, using distributed acoustic sensing (DAS). We record both the amplitude and frequency of seafloor strains induced by ocean surface gravity waves, as well as secondary microseisms caused by the interaction of gravity waves incident and reflected from the coast. By leveraging the spatially distributed nature of DAS measurements, additional fundamental information is recovered such as the velocity and azimuth of the waves. We find that on average 30 per cent of the gravity waves are reflected at the coast generating local sources of secondary microseisms that manifest as Scholte waves. These local sources represent the most energetic contribution to the seismic noise recorded along the OF and by an onshore broad-band station located near the DAS interrogator. Furthermore, we estimate a coastal reflection coefficient of ocean surface gravity waves R2 of about 0.07, which provides improved constraints for seismic noise generation models. In addition, we show that new local sources of microseisms can be generated when gravity waves characteristics (azimuth and frequency content) change and lead to some delays between the OF cable and buoy recordings. These analyses pave the way for a wide use of DAS data to monitor ocean–solid earth interactions as they provide a wealth of information on the reflection of gravity waves, coastal microseismic sources, and new constraints for numerical models of microseismic noise.
The fungal elicitor eutypine from Eutypa lata activates basal immunity through its phenolic side chains
Authors: Guan Pingyin , Schmidt Florian , Fischer Jochen , Riemann Michael , Thines Eckhard , Nick Peter
Published: June 2022

Grapevine trunk diseases (GTDs) affect grape production and reduce vineyard longevity worldwide. Since the causative fungi also occur in asymptomatic trunks, we address disease outbreak in terms of altered chemical communication between host and endophyte. Here, we identified four chemically similar secondary metabolites secreted by the GTD-associated fungus Eutypa lata to analyse their modes of action in a grapevine cell culture of Vitis rupestris, where microtubules were tagged by GFP. Treatment with the metabolite eutypine activated defence responses, evident from extracellular alkalinisation and induction of defence genes. Eutypinol, instead, eliminated microtubules, in contrast to the other three compounds. Furthermore, we evaluated the effect of four corresponding chemical analogues of these compounds, sharing the phenolic but lacking the alkyne moiety. These analogues were able to induce similar defence responses in V. rupestris cells, albeit at reduced amplitude. Since closely related moieties differing only in details of the side groups at the phenolic ring differ significantly with respect to the response of the host cell, we propose that these fungal compounds act through a specific binding site at the membrane of grapevine cells. We corroborate this specificity by combination experiments, where the eutypine and the eutypinol analogues behave competitively with respect to the elicited responses. In summary, Eutypa lata secretes compounds that elicit host defence in a specific manner by interfering with early events of immunity signalling. This supports the notion that a real understanding of GTDs has to address inter-organismic chemical communication.
O03 ST97 Staphylococcus aureus and oxacillin resistance: an emerging challenge for microbiologists?
Authors: Hughes G , Li D , Kerrigan R , Gupta I , Wilkinson S
Published: June 2022

Background

The presence of cefoxitin and oxacillin resistance in Staphylococcus aureus isolates is suggestive of methicillin resistance (MRSA) with molecular detection of the mecA or mecC genes providing confirmation. The UK SMI and EUCAST guidelines for MRSA detection describe a subset of strains that exhibit reduced susceptibility to oxacillin and cefoxitin, though negative for mecA and mecC genes—frequently named borderline oxacillin-resistant S. aureus (BORSA). Local data noted a number of S. aureus isolates that matched the above phenotype leading to laboratory, clinical and epidemiological questions.

Methods

Routine samples were collected between August 2020 and April 2021 at West Midlands Health Security Agency Laboratory, Birmingham. If provisional results suggested an MRSA isolate, the following confirmatory tests were undertaken. Locally, clinical samples underwent susceptibility testing with cefoxitin disc diffusion and oxacillin gradient diffusion (MRSA screens) or Vitek 2 (non-MRSA screens). Isolates with discrepant results [susceptible to cefoxitin; resistant to oxacillin (MIC >2 mg/L) or vice versa] were sent to the reference laboratory at Colindale, UK for further testing, which included mecA or mecC gene detection by PCR and serotyping with Illumina sequencing for all isolates.

Results

In total, 53 isolates were sent to the reference lab of which 22 were confirmed to have an ST97 serotype. All 53 were negative by PCR for mecA and mecC genes. For the 22 isolates of ST97, local oxacillin MIC values ranged from 2 to 6 mg/L. Cefoxitin susceptibility was confirmed locally in all isolates. The 22 isolates were from 15 patients; wound swabs (n = 18); blood culture (n = 1), sputum (n = 1) and MRSA screen (n = 2). Median patient age was 48 years (IQR 38–59) with 5 being female and 10 male. A history of injecting drug use was documented in 53% (8/15).

Conclusions

BORSA remains a problem from a laboratory, clinical and infection control perspective. This work raises two important questions: what is the most appropriate local laboratory testing pathway and what is the clinical relevance of these isolates (i.e. can flucloxacillin be relied upon in treatment)? The ST97 serotype appears to be associated with skin and soft tissue infection and may be linked to people who inject drugs.
P03 Improving antimicrobial stewardship and sustainability by promoting oral metronidazole in eligible surgical patients at the Royal Alexandra Hospital
Authors: Rodger Rachael , Robertson Amy , McGee Caroline , Chisholm Lindsey , Ballantyne Helen , McCutcheon Claire
Published: June 2022

Background

Antimicrobial stewardship (AS) is essential to minimize the emergence and spread of antimicrobial resistance.1 Timely IV to oral antibiotic switch and promotion of the oral route are key AS initiatives in the acute hospital setting.1 Metronidazole is commonly prescribed IV in the surgical management of intra-abdominal sepsis; however, metronidazole has excellent oral bioavailability of 95%–100%. In addition to improved AS, the oral route provides advantages to patients, staff and the environment including reduced patient risk of line infections/complications; reduced staff workload and healthcare costs; improved patient comfort/mobility; earlier discharge; and improved sustainability.

Objectives

To measure baseline proportion of surgical patients meeting the criteria for oral receiving oral metronidazole; introduce tests of change to promote use of oral metronidazole where appropriate; and measure changes in prescribing behaviour to determine if improvement has been achieved, with the aim of increasing the proportion of oral metronidazole prescribed to eligible Royal Alexandra Hospital (RAH) surgical patients to 50% by February 2022.

Methods

Baseline metronidazole prescribing data were collected over 6 weeks in surgical wards at the RAH. Exclusions for oral metronidazole included compromised gut absorption, oral route unreliable or worsening clinical condition/sepsis. A quality improvement approach was used to engage and raise awareness of the multidisciplinary surgical team to the benefits of prescribing oral metronidazole where appropriate. A range of methods were used including prospective audit and feedback; departmental presentations to surgical and pharmacy teams; eye-catching posters in key areas; staff champions; staff recognition awards; WhatsApp© group messages; and West of Scotland Surgical Association presentation. To measure improvement the proportion of oral and IV metronidazole prescribed was measured weekly and oral and IV metronidazole usage data in RAH surgical wards was measured monthly. A questionnaire was used to assess the impact of the project on nursing staff.

Results

Baseline data (n = 90) highlighted that only 13.5% of patients meeting the criteria for oral metronidazole were prescribed oral in RAH surgical wards. Post-change: oral metronidazole prescribing increased from a baseline median of 7% to 51%; IV metronidazole usage data decreased by 45%; there were 320 fewer IV metronidazole administrations per month; and nursing staff reported benefits including reduced workload, improved patient comfort and reduced plastic waste.

Conclusions

A quality improvement approach to engage and raise staff awareness of the benefits of oral metronidazole resulted in a change in prescribing behaviour and increased the proportion of oral metronidazole prescribed to eligible surgical patients to 50% by February 2022.
P08 The difficulty of Pseudomonas aeruginosa eradication in a post-spinal anaesthesia meningitis
Authors: Kolovani Entela , Ramosaço Ergys , Xhumari Artur , Kryemadhi Nevila , Harxhi Arjan , Çomo Najada
Published: June 2022

Background

Meningitis and ventriculitis due to Pseudomonas aeruginosa are uncommon. They are commonly secondary hospital-onset and typically related to neurosurgical procedure. Previous studies have shown P. aeruginosa to be responsible for 1%–18% of nosocomial meningitis cases. Both treatment failure and relapses are known to occur, and the recorded mortality is high, approaching 80% in some studies.

Objectives

We report a case of P. aeruginosa meningitis in a 26-year-old woman following spinal anaesthesia for caesarean section, its clinical characteristics, treatment challenges in the era of high generation antibiotics and the outcomes.

Results

A 26-year-old woman was hospitalized after 1 week of her third child delivery by caesarean section with spinal anaesthesia and 3 days after high fever and headache. Lumbar puncture was performed immediately, and leucocyte cell count was 723 cell/dL with 94% segmented neutrophils. CSF glucose was very low, and protein was 420 mg/dL. P. aeruginosa was isolated and it was susceptible to all antibiotics of standard panel. Cranial and lumbar region CT scans were normal. We modified empirical treatment and started ceftazidime and gentamicin. Three days after de-hospitalization in improved condition, she had high fever and strong headache and came back to hospital. We started treatment with imipenem and ciprofloxacin and 2 months after we performed several lumbar punctures, cranial MRIs and changed different antibiotic regimens with third generation cephalosporins, aminoglycosides, carbapenems and colistin; her clinical situation such as headache and fever and CSF did not show any sign of improvement. Susceptible P. aeruginosa was isolated each time we examined her CSF. She decided to leave the hospital and 2 weeks after her headache worsened and a convulsive attack happened. The cranial MRI showed hydrocephaly and a white precipitate (pus) in the left lateral ventricle. An extraventricular drain helped to resolve hydrocephaly and intraventricular colistin was injected until CSF was sterilized. After 1 month she was in a very good condition and a ventriculo-peritoneal shunt was placed.

Conclusions

P. aeruginosa meningitis was associated with some treatment difficulties. Even after an early nosological and microbiological diagnosis and an appropriate choice of antibiotics, based on bacterial meningitis treatment criteria and antibiogram, we couldn't eradicate the bacteria from CSF. To achieve success in this nosocomial infection from a not careful asepsis, sometimes a prolonged antibiotic and local treatment with intraventricular or intrathecal therapy is needed.
Automated medical literature screening using artificial intelligence: a systematic review and meta-analysis
Authors: Feng Yunying , Liang Siyu , Zhang Yuelun , Chen Shi , Wang Qing , Huang Tianze , Sun Feng , Liu Xiaoqing , Zhu Huijuan , Pan Hui
Published: June 2022

Objective

We aim to investigate the application and accuracy of artificial intelligence (AI) methods for automated medical literature screening for systematic reviews.

Materials and Methods

We systematically searched PubMed, Embase, and IEEE Xplore Digital Library to identify potentially relevant studies. We included studies in automated literature screening that reported study question, source of dataset, and developed algorithm models for literature screening. The literature screening results by human investigators were considered to be the reference standard. Quantitative synthesis of the accuracy was conducted using a bivariate model.

Results

Eighty-six studies were included in our systematic review and 17 studies were further included for meta-analysis. The combined recall, specificity, and precision were 0.928 [95% confidence interval (CI), 0.878–0.958], 0.647 (95% CI, 0.442–0.809), and 0.200 (95% CI, 0.135–0.287) when achieving maximized recall, but were 0.708 (95% CI, 0.570–0.816), 0.921 (95% CI, 0.824–0.967), and 0.461 (95% CI, 0.375–0.549) when achieving maximized precision in the AI models. No significant difference was found in recall among subgroup analyses including the algorithms, the number of screened literatures, and the fraction of included literatures.

Discussion and Conclusion

This systematic review and meta-analysis study showed that the recall is more important than the specificity or precision in literature screening, and a recall over 0.95 should be prioritized. We recommend to report the effectiveness indices of automatic algorithms separately. At the current stage manual literature screening is still indispensable for medical systematic reviews.
Digital Health Applications in Oncology: An Opportunity to Seize
Authors: Parikh Ravi B , Basen-Enquist Karen M , Bradley Cathy , Estrin Deborah , Levy Mia , Lichtenfeld J Leonard , Malin Bradley , McGraw Deven , Meropol Neal J , Oyer Randall A , Sheldon Lisa Kennedy , Shulman Lawrence N
Published: June 2022

Digital health advances have transformed many clinical areas including psychiatric and cardiovascular care. However, digital health innovation is relatively nascent in cancer care, which represents the fastest growing area of health-care spending. Opportunities for digital health innovation in oncology include patient-facing technologies that improve patient experience, safety, and patient-clinician interactions; clinician-facing technologies that improve their ability to diagnose pathology and predict adverse events; and quality of care and research infrastructure to improve clinical workflows, documentation, decision support, and clinical trial monitoring. The COVID-19 pandemic and associated shifts of care to the home and community dramatically accelerated the integration of digital health technologies into virtually every aspect of oncology care. However, the pandemic has also exposed potential flaws in the digital health ecosystem, namely in clinical integration strategies; data access, quality, and security; and regulatory oversight and reimbursement for digital health technologies. Stemming from the proceedings of a 2020 workshop convened by the National Cancer Policy Forum of the National Academies of Sciences, Engineering, and Medicine, this article summarizes the current state of digital health technologies in medical practice and strategies to improve clinical utility and integration. These recommendations, with calls to action for clinicians, health systems, technology innovators, and policy makers, will facilitate efficient yet safe integration of digital health technologies into cancer care.
Appendiceal diverticulum masquerading as acute appendicitis
Authors: Patel A , Abbas A , Bhattacharyya R , Galaktionova D
Published: June 2022

Appendiceal diverticula present as rare clinical finding and are most confused with acute appendicitis. A 65-year-old female was presented to our surgical service after 1 day of right lower quadrant abdominal pain and a computed tomography evaluation, read as a diagnosis of acute appendicitis. Due to the location and quality of pain and intraoperative findings acute appendicitis was our preliminary diagnosis. Follow up with histopathology confirmed acute inflammation of an appendiceal diverticulum. With discordance in original diagnosis from final pathological evaluation, we suggest appendiceal diverticula as an important differential to consider in patients of similar clinical presentation. Surgical treatment with appendectomy and final histological diagnosis are essential in the proper treatment of this rare clinical finding.
Pseudo-intestinal obstruction after transsphenoidal surgery for craniopharyngioma
Authors: Ohta Jo , Kadoi Yuji , Tosaka Masahiko , Saito Shigeru
Published: June 2022

Craniopharyngioma surgery is frequently associated with the occurrence of central diabetes insipidus, and oral rehydration therapy is reliable for postoperative management if the patient’s thirst is normal. A 61-year-old Japanese male patient underwent extended endoscopic transsphenoidal surgery for craniopharyngioma. He was undergoing acute treatment for postoperative central diabetes insipidus and hypopituitarism in the intensive care unit. Two days after the surgery, he started to vomit occasionally, despite receiving oral rehydration therapy for central diabetes insipidus. Despite increasing the dose of parenteral hydrocortisone, the periodic vomiting persisted during fasting periods and progressed to aspiration pneumonia and severe sepsis. Abdominal computed tomography was performed to identify the cause of persistent vomiting and revealed the presence of a pseudo-intestinal obstruction extending from the small to large intestine. When oral rehydration therapy for central diabetes insipidus is accompanied by vomiting symptoms suggestive of hypopituitarism, a holistic evaluation of the gastrointestinal system is advisable.
Decoding the antifungal resistance mechanisms in biofilms of emerging, ubiquitous and multidrug-resistant species belonging to the Scedosporium/Lomentospora genera
Authors: Mello Thaís P , Oliveira Simone S C , Branquinha Marta H , Santos André L S
Published: June 2022

The opportunistic filamentous fungi belonging to the Scedosporium and Lomentospora genera are highly tolerant to all classes of available antifungal drugs. Moreover, the mature biofilm formed by these fungi presents higher antifungal resistance when compared to planktonic cells. Nevertheless, the resistance mechanisms developed by the biofilm lifestyle are not completely elucidated. In the current study, we have investigated the mainly known resistance mechanisms to azoles (voriconazole and fluconazole) and polyenes (amphotericin B [AMB]) in S. apiospermum, S. minutisporum, S. aurantiacum, and L. prolificans (formerly S. prolificans) biofilms. Both classes of antifungals can physically bind to the extracellular matrix of mature biofilms, preventing the drugs from reaching their targets on biofilm-forming cells, which precludes their activity and toxicity. In addition, the activity of efflux pumps, measured by Rhodamine 6 G, was increased along with the maturation of the biofilm. The efflux pump's inhibition by L-Phe-L-Arg-β-naphthylamide culminated in a 2- to 16-fold increase in azole susceptibility in conidial cells, but not in mature biofilms. Finally, we demonstrated by using specific inhibitors that in conidia, but not in biofilms, AMB induced the production of reactive oxygen species through the activity of the oxidative phosphorylation system (complex I–IV and alternative oxidases). However, the cellular redox imbalance caused by AMB was well-coped with the high activity of antioxidative enzymes, such as superoxide dismutase and catalase. Altogether, our results revealed that Scedosporium/Lomentospora biofilm resistance occurs through various mechanisms that operate concomitantly, which could explain the huge challenge in the clinical treatment of scedosporiosis/lomentosporiosis.

Lay Summary

Scedosporium/Lomentospora spp. are multidrug-resistant pathogens able to cause diverse types of infections with typical biofilm characteristics, which makes the treatment a hard issue. We deciphered the resistance mechanisms to classical antifungals developed in the biofilm formed by these fungi.
Creating jackknife and bootstrap estimates of the covariance matrix for the two-point correlation function
Authors: Mohammad Faizan G , Percival Will J
Published: June 2022

We present correction terms that allow delete-one Jackknife and Bootstrap methods to be used to recover unbiased estimates of the data covariance matrix of the two-point correlation function $\xi \left(\mathbf {r}\right)$. We demonstrate the accuracy and precision of this new method using a large set of 1000 QUIJOTE simulations that each cover a comoving volume of $1\rm {\left[h^{-1}Gpc\right]^3}$. The corrected resampling techniques recover the correct amplitude and structure of the data covariance matrix as represented by its principal components to within ∼10 per cent, the level of error achievable with the size of the sample of simulations used for the test. Our corrections for the internal resampling methods are shown to be robust against the intrinsic clustering of the cosmological tracers both in real- and redshift space using two snapshots at z = 0 and z = 1 that mimic two samples with significantly different clustering. We also analyse two different slicing of the simulation volume into $\, n_{\rm sv}\, =64$ or 125 sub-samples and show that the main impact of different $\, n_{\rm sv}\,$ is on the structure of the covariance matrix due to the limited number of independent internal realizations that can be made given a fixed $\, n_{\rm sv}\,$.
Optical polarization signatures of black hole X-ray binaries
Authors: Kravtsov Vadim , Berdyugin Andrei V , Kosenkov Ilia A , Veledina Alexandra , Piirola Vilppu , Qadir Yasir Abdul , Berdyugina Svetlana V , Sakanoi Takeshi , Kagitani Masato , Poutanen Juri
Published: June 2022

Polarimetry provides an avenue for probing the geometry and physical mechanisms producing optical radiation in many astrophysical objects, including stellar binary systems. We present the results of multiwavelength (BVR) polarimetric studies of a sample of historical black hole X-ray binaries, observed during their outbursts or in the quiescent (or near-quiescent) state. We surveyed both long- and short-period systems, located at different Galactic latitudes. We performed careful analysis of the interstellar polarization in the direction on the sources to reliably estimate the intrinsic source polarization. Intrinsic polarization was found to be small (<0.2 per cent) in sources observed in bright soft states (MAXI J0637−430 and 4U 1957+115). It was found to be significant in the rising hard state of MAXI J1820+070 at the level of ∼0.5 per cent and negligible in the decaying hard state and during its failed outbursts, while Swift J1357.2−0933  showed its absence in the rising hard state. Three (XTE J1118+480 , V4641 Sgr , V404 Cyg) sources observed during quiescence show no evidence of significant intrinsic polarization, while MAXI J1820+070  is the only black hole X-ray binary which showed substantial (>5 per cent) intrinsic quiescent-state polarization with a blue spectrum. The absence of intrinsic polarization at the optical wavelengths puts constraints on the potential contribution of non-stellar (jet, hot flow, accretion disc) components to the total spectra of black hole X-ray binaries.
A galaxy-free phenomenological model for the 21-cm power spectrum during reionization
Authors: Mirocha Jordan , Muñoz Julian B , Furlanetto Steven R , Liu Adrian , Mesinger Andrei
Published: June 2022

Upper limits from the current generation of interferometers targeting the 21-cm signal from high redshifts have recently begun to rule out physically realistic, though still extreme, models of the Epoch of Reionization (EoR). While inferring the detailed properties of the first galaxies is one of the most important motivations for measuring the high-z 21-cm signal, they can also provide useful constraints on the properties of the intergalactic medium (IGM). Motivated by this, we build a simple, phenomenological model for the 21-cm power spectrum that works directly in terms of IGM properties, which bypasses the computationally expensive 3D semi-numerical modeling generally employed in inference pipelines and avoids explicit assumptions about galaxy properties. The key simplifying assumptions are that (i) the ionization field is binary, and composed of spherical bubbles with an abundance described well by a parametric bubble size distribution, and (ii) that the spin temperature of the ‘bulk’ IGM outside bubbles is uniform. Despite the simplicity of the model, the mean ionized fraction and spin temperature of the IGM recovered from mock 21-cm power spectra generated with 21cm fast are generally in good agreement with the true input values. This suggests that it is possible to obtain comparable constraints on the IGM using models with very different assumptions, parameters, and priors. Our approach will thus be complementary to semi-numerical models as upper limits continue to improve in the coming years.
Mechanism of transcription modulation by the transcription-repair coupling factor
Authors: Paudel Bishnu P , Xu Zhi-Qiang , Jergic Slobodan , Oakley Aaron J , Sharma Nischal , Brown Simon H J , Bouwer James C , Lewis Peter J , Dixon Nicholas E , van Oijen Antoine M , Ghodke Harshad
Published: June 2022

Elongation by RNA polymerase is dynamically modulated by accessory factors. The transcription-repair coupling factor (TRCF) recognizes paused/stalled RNAPs and either rescues transcription or initiates transcription termination. Precisely how TRCFs choose to execute either outcome remains unclear. With Escherichia coli as a model, we used single-molecule assays to study dynamic modulation of elongation by Mfd, the bacterial TRCF. We found that nucleotide-bound Mfd converts the elongation complex (EC) into a catalytically poised state, presenting the EC with an opportunity to restart transcription. After long-lived residence in this catalytically poised state, ATP hydrolysis by Mfd remodels the EC through an irreversible process leading to loss of the RNA transcript. Further, biophysical studies revealed that the motor domain of Mfd binds and partially melts DNA containing a template strand overhang. The results explain pathway choice determining the fate of the EC and provide a molecular mechanism for transcription modulation by TRCF.
CRISPR-mediated protein-tagging signal amplification systems for efficient transcriptional activation and repression inSaccharomyces cerevisiae
Authors: Zhai Haotian , Cui Li , Xiong Zhen , Qi Qingsheng , Hou Jin
Published: June 2022

Saccharomyces cerevisiae is an important model eukaryotic microorganism and widely applied in fundamental research and the production of various chemicals. Its ability to efficiently and precisely control the expression of multiple genes is valuable for metabolic engineering. The clustered regularly interspaced short palindromic repeats (CRISPR)-mediated regulation enables complex gene expression programming; however, the regulation efficiency is often limited by the efficiency of pertinent regulators. Here, we developed CRISPR-mediated protein-tagging signal amplification system for simultaneous multiplexed gene activation and repression in S. cerevisiae. By introducing protein scaffolds (SPY and SunTag systems) to recruit multiple copies of regulators to different nuclease-deficient CRISPR proteins and design optimization, our system amplified gene regulation efficiency significantly. The gene activation and repression efficiencies reached as high as 34.9-fold and 95%, respectively, being 3.8- and 8.6-fold higher than those observed on the direct fusion of regulators with nuclease-deficient CRISPR proteins, respectively. We then applied the orthogonal bifunctional CRISPR-mediated transcriptional regulation system to regulate the expression of genes associated with 3-hydroxypropanoic acid production to deduce that CRISPR-associated regulator recruiting systems represent a robust method for simultaneously regulating multiple genes and rewiring metabolic pathways.
KDM6B promotes PARthanatos via suppression of O6-methylguanine DNA methyltransferase repair and sustained checkpoint response
Authors: Yang Mingming , Wang Chenliang , Zhou Mi , Bao Lei , Wang Yanan , Kumar Ashwani , Xing Chao , Luo Weibo , Wang Yingfei
Published: June 2022

Poly(ADP-ribose) polymerase-1 (PARP-1) is a DNA damage sensor and contributes to both DNA repair and cell death processes. However, how PARP-1 signaling is regulated to switch its function from DNA repair to cell death remains largely unknown. Here, we found that PARP-1 plays a central role in alkylating agent-induced PARthanatic cancer cell death. Lysine demethylase 6B (KDM6B) was identified as a key regulator of PARthanatos. Loss of KDM6B protein or its demethylase activity conferred cancer cell resistance to PARthanatic cell death in response to alkylating agents. Mechanistically, KDM6B knockout suppressed methylation at the promoter of O6-methylguanine-DNA methyltransferase (MGMT) to enhance MGMT expression and its direct DNA repair function, thereby inhibiting DNA damage-evoked PARP-1 hyperactivation and subsequent cell death. Moreover, KDM6B knockout triggered sustained Chk1 phosphorylation and activated a second XRCC1-dependent repair machinery to fix DNA damage evading from MGMT repair. Inhibition of MGMT or checkpoint response re-sensitized KDM6B deficient cells to PARthanatos induced by alkylating agents. These findings provide new molecular insights into epigenetic regulation of PARP-1 signaling mediating DNA repair or cell death and identify KDM6B as a biomarker for prediction of cancer cell vulnerability to alkylating agent treatment.
CALCIUM-DEPENDENT PROTEIN KINASE38 regulates flowering time and common cutworm resistance in soybean
Authors: Li Xiao , Hu Dezhou , Cai Linyan , Wang Huiqi , Liu Xinyu , Du Haiping , Yang Zhongyi , Zhang Huairen , Hu Zhenbin , Huang Fang , Kan Guizhen , Kong Fanjiang , Liu Baohui , Yu Deyue , Wang Hui
Published: June 2022

Photoperiod-sensitive plants such as soybean (Glycine max) often face threats from herbivorous insects throughout their whole growth period and especially during flowering; however, little is known about the relationship between plant flowering and insect resistance. Here, we used gene editing, multiple omics, genetic diversity and evolutionary analyses to confirm that the calcium-dependent protein kinase GmCDPK38 plays a dual role in coordinating flowering time regulation and insect resistance of soybean. Haplotype 2 (Hap2)-containing soybeans flowered later and were more resistant to the common cutworm (Spodoptera litura Fabricius) than those of Hap3. gmcdpk38 mutants with Hap3 knocked out exhibited similar flowering and resistance phenotypes as Hap2. Knocking out GmCDPK38 altered numerous flowering- and resistance-related phosphorylated proteins, genes, and metabolites. For example, the S-adenosylmethionine synthase GmSAMS1 was post-translationally upregulated in the gmcdpk38 mutants. GmCDPK38 has abundant genetic diversity in wild soybeans and was likely selected during soybean domestication. We found that Hap2 was mostly distributed at low latitudes and had a higher frequency in cultivars than in wild soybeans, while Hap3 was widely selected at high latitudes. Overall, our results elucidated that the two distinct traits (flowering time and insect resistance) are mediated by GmCDPK38.
«L’égalité entre les associés-coopérateurs en droit de l’OHADA»
Authors: Kontchop Hilarion
Published: June 2022

This study focuses on the equality among cooperative shareholders under the OHADA2 law. It analyses, with regards to the specificity of cooperative companies; the place that OHADA legislature gives to the general principle of equality in cooperative structures. It shows from our analysis that the principle of equality in partners has not only been taken up by the legislature in the Uniform Act on cooperatives, but that it has also been strengthened giving the specificity of cooperative structures.
Laminin N‐terminus α31 expression during development is lethal and causes widespread tissue‐specific defects in a transgenic mouse model
Authors: Sugden Conor J. , Iorio Valentina , Troughton Lee D. , Liu Ke , Morais Mychel R. P. T. , Lennon Rachel , Bou‐Gharios George , Hamill Kevin J.
Published: June 2022

Laminins (LMs) are essential components of all basement membranes where they regulate an extensive array of tissue functions. Alternative splicing from the laminin α3 gene produces a non‐laminin but netrin‐like protein, Laminin N terminus α31 (LaNt α31). LaNt α31 is widely expressed in intact tissue and is upregulated in epithelial cancers and during wound healing. In vitro functional studies have shown that LaNt α31 can influence numerous aspects of epithelial cell behavior via modifying matrix organization, suggesting a new model of laminin auto‐regulation. However, the function of this protein has not been established in vivo. Here, a mouse transgenic line was generated using the ubiquitin C promoter to drive inducible expression of LaNt α31. When expression was induced at embryonic day 15.5, LaNt α31 transgenic animals were not viable at birth, exhibiting localized regions of erythema. Histologically, the most striking defect was widespread evidence of extravascular bleeding across multiple tissues. Additionally, LaNt α31 transgene expressing animals exhibited kidney epithelial detachment, tubular dilation, disruption of the epidermal basal cell layer and of the hair follicle outer root sheath, and ~50% reduction of cell numbers in the liver, associated with depletion of hematopoietic erythrocytic foci. These findings provide the first in vivo evidence that LaNt α31 can influence tissue morphogenesis.
HPV-57 Verruca Vulgaris Mimicking Epidermodysplasia Verruciformis
Authors: Kirchner Allison , Jaros Joanna , Braniecki Marylee , Nuovo Gerard , Mehta Shilpa
Published: June 2022

Human papilloma virus (HPV) is the causative agent for a variety of cutaneous lesions including verruca vulgaris (VV) and epidermodysplasia verruciformis (EDV). There are more than 200 known genotypes of HPV, and specific HPV types are associated with different clinical manifestations and malignant potentials. Herein, we describe a case of a 43-year-old immunocompetent woman who presented with morphologically distinct lesions that were most consistent with EDV on clinical examination. However, further histopathological and viral analysis confirmed the lesions as HPV-57–positive VV. The risk of malignant transformation, and therefore treatment and surveillance, is dramatically different in VV versus EDV. Therefore, this case highlights the importance of a proper histopathological diagnosis with HPV viral testing when clinical presentations may vary or mimic other diseases.
THE ROLE OF OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY IN PATIENTS WITH PREECLAMPSIA
Authors: Özcan Zeynep Özer , Güngör Kıvanç , Saygili Oğuzhan , Özcan Hüseyin Çağlayan
Published: June 2022

Purpose:

To investigate the changes in the microvascular structure of the retina and optic disk by comparing the optical coherence tomography angiography findings in preeclamptic patients with those in healthy pregnant women and healthy nonpregnant women and also to evaluate the preeclamptic patients after delivery by showing whether the changes are permanent or not.

Methods:

Fifty preeclamptic, 50 healthy pregnant, and 50 healthy nonpregnant women enrolled in three groups (preeclamptic pregnant women group, healthy pregnant women group, and nonpregnant women group; respectively). Patients in the preeclamptic pregnant women group were evaluated at three different time points including up to 3 hours before delivery (Group 1), 2, or 3 days after delivery (Group 2), and 6 weeks after delivery (Group 3), and compared with each other. All patients underwent a comprehensive ophthalmologic examination including optical coherence tomography angiography.

Results:

Choriocapillaris blood flow area, deep foveal density, deep temporal density, deep nasal density, and radial peripapillary capillary inside disk density values were significantly lower in the preeclamptic pregnant women group than in the healthy pregnant women group. Deep foveal density and deep nasal density values were significantly higher in Group 3 than in Group 1 and 2, and deep temporal density was significantly higher in Group 3 than in Group 1.

Conclusion:

Optical coherence tomography angiography diagnosed decreased deep retinal capillary density values in the macula of patients with preeclampsia, but these results improved after delivery.
INCREASED DISTANCE FROM THE CLINIC LEADS TO HIGHER LOSS TO FOLLOW-UP AFTER PARS PLANA VITRECTOMY IN DIABETIC PATIENTS
Authors: Deans John R. , George Roshan , Aldaas Khalid , Van Buren Eric D. , Ulrich J. Niklas
Published: June 2022

Purpose:

The importance of consistent outpatient follow-up for management of diabetic eye disease has been well-established. The objective of this study was to identify patient factors associated with being lost to follow-up in postsurgical patients after undergoing pars plana vitrectomy for diabetic eye disease.

Methods:

The charts of diabetic patients undergoing pars plana vitrectomy for nonclearing vitreous hemorrhage at an academic medical center by a single surgeon between 2012 and 2019 were reviewed. The rates of loss to follow-up during the postoperative period were compared based on patient distance from the clinic and insurance status.

Results:

A total of 144 patients met inclusion criteria. A total of 45 patients (31.25%) were lost to follow-up during the 3-month postoperative period. The rate of loss to follow-up increased with every postoperative visit and was significantly higher for patients living greater than 30 miles from the clinic versus patients living within 30 miles from the clinic. There was no statistically significant difference in loss to follow-up based on insurance status.

Conclusion:

Increased distance from the clinic presents a challenge to providing safe and effective postsurgical care to diabetic patients. This presents opportunities for comanagement or other creative strategies to improve postsurgical follow-up rates for at-risk patients.
Thirty-Day Readmission Among Patients With Uncomplicated Choledocholithiasis
Authors: Wang Yichen , Murphy Dermot , Li Si , Chen Bing , Peluso Heather , Sondhi Vikram , Abougergi Marwan S.
Published: June 2022

Background and Aim:

We aimed to determine the rate of 30-day hospital readmissions of uncomplicated choledocholithiasis and its impact on mortality and health care use in the United States.

Methods:

Nonelective admissions for adults with uncomplicated choledocholithiasis were selected from the Nationwide Readmission Database 2016-2018. The primary outcome was the all-cause 30-day readmission rate. Secondary outcomes were reasons for readmission, readmission mortality rate, procedures, and resource use (length of stay and total hospitalization costs and charges). Independent risk factors for readmission were identified using Cox regression analysis.

Results:

The 30-day rate of readmission was 9.3%. Biliary and pancreatic disorders and postprocedural complications accounted for 36.6% and 10.3% of readmission, respectively. The mortality rate among patients readmitted to the hospital was higher than that for index admissions (2.0% vs. 0.4%, P<0.01). Readmitted patients were less likely to receive endoscopic retrograde cholangiopancreatography (61% vs. 69%, P<0.01) and laparoscopic cholecystectomy (12.5% vs. 26%, P<0.01) during the index admissions. A total of 42,150 hospital days was associated with readmission, and the total health care in-hospital economic burden was $112 million (in costs) and $470 million (in charges). Independent predictors of readmission were male sex, Medicare (compared with private) insurance, higher Elixhauser Comorbidity Index score, no endoscopic retrograde cholangiopancreatography or laparoscopic cholecystectomy, postprocedural complications of the digestive system, hemodynamic or respiratory support, urban hospitals, and lower hospital volume of uncomplicated choledocholithiasis.

Conclusions:

The uncomplicated choledocholithiasis 30-day readmission rate is 9.3%. Readmission was associated with higher mortality, morbidity, and resource use. Multiple independent predictors of readmission were identified.