bluuebunny/crossref_metadata_2025 huggingface dataset:
How to prevent postoperative ileus in colorectal surgery? a systematic review
Authors: Chaouch Mohamed Ali , Daghmouri Mohamed Aziz , Lahdheri Abdallah , Hussain Mohammad Iqbal , Nasri Salsabil , Gouader Amine , Noomen Faouzi , Oweira Hani
Published: September 2023

Postoperative ileus (PI) after colorectal surgery is a common surgical problem. This systematic review aimed to investigate the available data in the literature to reduce the PI in the area of colorectal surgery out of the enhanced recovery after surgery principles, referring to published randomized controlled trials (RCTs) and meta-analyses, and to provide recommendations according to the Oxford Centre for Evidence-Based Medicine. The authors conducted bibliographic research on 1 December 2022. The authors retained meta-analyses and RCTs. The authors concluded that when we combined colonic mechanical preparation with oral antibiotic decontamination, the authors found a significant reduction in PI. The open approach was associated with a higher PI rate. The robotic and laparoscopic approaches had similar PI rates. Low ligation of the inferior mesenteric artery presented a PI similar to that of high ligation of the inferior mesenteric artery. There was no difference between the isoperistaltic and antiperistaltic anastomoses or between the intracorporeal and extracorporeal anastomoses. This study summarized the available data in the literature, including meta-analyses and RCTs. For a higher level of evidence, additional multicenter RCTs and meta-analyses of RCTs remain necessary.
Giant right atrial myxoma presented with symptoms of Budd–Chiari syndrome: a case report
Authors: Med Sidi El Moctar Echreiva , El Hadj Sidi Chighaly , Abdulrazzak Mohammed , Ahmed Kamal Manar , Mohamed Ahmed Mohamed Feissal , Boye Khaled
Published: September 2023

Introduction and importance:

Right atrial myxoma is rarely associated with Budd–Chiari syndrome (BCS). In this paper, we present a case of a young patient with a giant right atrial myxoma complicated by the development of BCS.

Case presentation:

A 26-year-old female presented to the emergency room with persistent abdominal pain, ascites, lower limb edema, and an acute episode of dyspnea. Abdominal computed tomography revealed a lesion in the right cardiac cavity that resembled an intracardiac thrombus. Transthoracic echocardiography showed a large heterogeneous mass in the right atrium protruding into the right ventricle and a large thrombus interfering with inferior vena cava flow. The patient underwent cardiac surgery to remove the atrial mass, and histopathologic examinations confirmed the diagnosis of atrial myxoma.

Clinical discussion:

The right atrial myxoma is relatively rare, especially the giant ones. Rarely have intracardiac tumors such as giant right atrial myxoma been identified as a risk factor for the onset of BCS.

Conclusion:

In the differential diagnosis of BCS, right atrial tumors, including myxomas, should be considered, especially when other explanations are absent.
Donor’s ability to comprehend and carefully assess the benefits and risks of donation in living donor liver transplantation: a Pakistani perspective – a short communication
Authors: Ullah Kaleem , Dogar Abdul W. , Ochani Sidhant , Ahmad Hafiz B. , Hasibuzzaman Md. Al
Published: September 2023

Patients unlikely to obtain deceased donor liver transplantation (DDLT) are offered living donor liver transplantation (LDLT) as an alternative. The success of LDLT is bound to the availability of altruistic donors who undergo smooth and safe surgery. Donor morbidity is reported to be up to 20–30%, while donor mortality is only 0.1–0.5%. Globally, LDLT poses numerous ethical concerns regarding living donors, such as autonomy, non-maleficence, and beneficence. The donor’s comprehension of information is a serious issue in LDLT. The donors may underestimate the risk of morbidity and mortality, as well as can ignore the long-term psychological consequences. Furthermore, donor voluntariness may be questionable as the donors may agree to donate under severe family pressure or emotional attachment. We propose open communication with all the donors, ensuring that they should not be subjected to any undue pressure or emotional lability. Donor knowledge and understanding of potential complications and the psychosocial aspect can be augmented by good communication. We also suggest that the donors’ education and psychological evaluation should be done in a friendly environment with complete privacy. Interventions should be aimed at improving communication and independent decision-making with the use of e-health educational tools for comprehension assessment.
A new modified limited incision for superficial parotidectomy compared to modified Blair’s incision
Authors: Alomar Omar Salem Khattab
Published: September 2023

Background:

Many incisions have been used to perform parotidectomy, but they result in a visible scar on the neck and may cause patient dissatisfaction by producing disfigurement sometimes.

Aim of Study:

The aim of this study is to use a modified limited incision for superficial parotidectomy as an alternative to the classical incision, with no obvious scarring and without affecting the identification of the facial nerve, resulting in better cosmesis.

Patients and Methods:

A prospective comparative study on 100 patients has undergone superficial parotidectomy using a modified limited incision and another 100 patients who have undergone superficial parotidectomy using the modified Blair’s incision (control group) for variant benign pathologies. The surgeries were conducted in four hospitals (three private and one public) in Baghdad, Iraq, from January 2016 to September 2022. In both groups, the patients were followed up through outpatient visits to assess the cosmetic result of the incision and detect postoperative complications.

Results:

All tumors were removed with no need for extending the skin incision. The cosmetic result of the incision was very satisfactory and only a nominal scar could be seen 6 months after surgery. Five percent of patients only developed postoperative complications.

Conclusion:

A modified limited incision for superficial parotidectomy provides better patient satisfaction compared to a modified Blair’s incision. The modified limited incision can be performed safely with a better cosmetic appearance of the surgical scar compared to the standard incision.
Establishment of hospital-based surgical residency programs as a health policy for surgical needs provision: an Indonesian perspective
Authors: Lukman Kiki
Published: September 2023

Objective:

One of the health interventions that can be implemented cost-effectively in developing countries is the provision of basic surgical procedures. One way to increase access to surgical services is to increase the production of surgeons, in this case through increasing the surgical residency program. There are similarities between university-based surgical residency programs and hospital-based surgical residency programs. However, in Indonesia, the differences between them are stark; the establishment of hospital-based surgical residency programs is challenging and requires collaboration between the government, university, college of surgery, and private sector.

Design:

The author reviewed the literature on post-graduate medical education for surgical programs and the contrast between university-based and hospital-based surgical residency programs.

Setting:

Information collected from the Indonesian Health Education Independent Accreditation Institution and varied literature was included.

Participants:

Not applicable.

Result:

In Indonesia, the implementation of an academic surgery environment in the hospital-based surgical residency program is challenging, and the implementation of the academic health system can increase student intake and provide more both from the university and the hospital-based surgical residency program.
Negotiated Rates for Surgical Cancer Care in the Era of Price Transparency—Prices Reflect Market Competition
Authors: Rochlin Danielle H. , Rizk Nada M. , Matros Evan , Wagner Todd H. , Sheckter Clifford C.
Published: September 2023

Objective:

To measure commercial price variation for cancer surgery within and across hospitals.

Summary Background Data:

Surgical care for solid organ tumors is costly and negotiated commercial rates have been hidden from public view. The Hospital Price Transparency Rule, enacted in 2021, requires all hospitals list their negotiated rates on their website, thus opening the door for an examination of pricing for cancer surgery.

Methods:

This was a cross-sectional study using 2021 negotiated price data disclosed US hospitals for the ten most common cancers treated with surgery. Price variation was measured using within- and across-hospital ratios. Commercial rates relative to cancer center designation and the Herfindahl-Hirschman Index at the facility level were evaluated with mixed effects linear regression with random intercepts per procedural code.

Results:

495,200 unique commercial rates from 2,232 hospitals resulted for the ten most common solid-organ tumor cancers. Gynecologic cancer operations had the highest median rates at $6,035.8/operation compared to bladder cancer surgery at $3,431.0/operation. Compared to competitive markets, moderately and highly concentrated markets were associated with significantly higher rates (HHI 1501-2500, coefficient $513.6, 95% CI, $295.5 - $731.7; HHI >2500, coefficient $1,115.5, 95% CI, $913.7–$1,317.2). National Cancer Institute designation was associated with higher rates, coefficient $3,451.9 (95% CI, -$2,853.2–$4,050.7).

Conclusions:

Commercial payer-negotiated prices for the surgical management of 10 common, solid-tumor malignancies varied widely both within and across hospitals. Higher rates were observed in less competitive markets. Future efforts should facilitate price competition and limit health market concentration.
Binocular vision and foraging in ducks, geese and swans (Anatidae)
Authors: Cantlay Jennifer C. , Martin Graham R. , McClelland Stephanie C. , Potier Simon , O'Brien Michelle F. , Fernández-Juricic Esteban , Bond Alexander L. , Portugal Steven J.
Published: September 2023

Wide variation in visual field configuration across avian species is hypothesized to be driven primarily by foraging ecology and predator detection. While some studies of selected taxa have identified relationships between foraging ecology and binocular field characteristics in particular species, few have accounted for the relevance of shared ancestry. We conducted a large-scale, comparative analysis across 39 Anatidae species to investigate the relationship between the foraging ecology traits of diet or behaviour and binocular field parameters, while controlling for phylogeny. We used phylogenetic models to examine correlations between traits and binocular field characteristics, using unidimensional and morphometric approaches. We found that foraging behaviour influenced three parameters of binocular field size: maximum binocular field width, vertical binocular field extent, and angular separation between the eye-bill projection and the direction of maximum binocular field width. Foraging behaviour and body mass each influenced two descriptors of binocular field shape. Phylogenetic relatedness had minimal influence on binocular field size and shape, apart from vertical binocular field extent. Binocular field differences are associated with specific foraging behaviours, as related to the perceptual challenges of obtaining different food items from aquatic and terrestrial environments.
Impairments in muscle shape changes affect metabolic demands duringin-vivocontractions
Authors: Monte Andrea , Zamparo Paola
Published: September 2023

The uncoupling behaviour between muscle belly and fascicle shortening velocity (i.e. belly gearing), affects mechanical output by allowing the muscle to circumvent the limits imposed by the fascicles' force-velocity relationship. However, little is known about the ‘metabolic effect' of a decrease/increase in belly gearing. In this study, we manipulated the plantar flexor muscles' capacity to change in shape (and hence belly gearing) by using compressive multidirectional loads. Metabolic, kinetic, electromyography activity and ultrasound data (in soleus and gastrocnemius medialis) were recorded during cyclic fixed-end contractions of the plantar flexor muscles in three different conditions: no load, +5 kg and +10 kg of compression. No differences were observed in mechanical power and electrophysiological variables as a function of compression intensity, whereas metabolic power increased as a function of it. At each compression intensity, differences in efficiency were observed when calculated based on fascicle or muscle behaviour and significant positive correlations (R2range: 0.7–0.8 andp> 0.001) were observed between delta efficiency (ΔEff: Effmus−Efffas) and belly gearing (Vmus/Vfas) or ΔV (Vmus−Vfas). Thus, changes in the muscles' capacity to change in shape (e.g. in muscle stiffness or owing to compressive garments) affect the metabolic demands and the efficiency of muscle contraction.
The resuscitation-promoting factor (Rpf) from Micrococcus luteus and its putative reaction product 1,6-anhydro-MurNAc increase culturability of environmental bacteria
Authors: Guzman Juan , Raval Dipansi , Hauck Dirk , Titz Alexander , Poehlein Anja , Degenkolb Thomas , Daniel Rolf , Vilcinskas Andreas
Published: September 2023

Bacterial dormant cells do not divide and are not immediately culturable, but they persist in a state of low metabolic activity, a physiological state having clinical relevance, for instance in latent tuberculosis. Resuscitation promoting factors (Rpf) are proteins that act as signaling molecules mediating growth and replication. In this study we aimed to test the effect of Rpf  from Micrococcus luteus on the number and diversity of cultured bacteria using insect and soil samples, and to examine if the increase in culturability could be reproduced with the putative reaction product of Rpf, 1,6-anhydro-MurNAc. The rpf gene from M. luteus was amplified and cloned into a pET21b expression vector and the protein was expressed in E. coli BL21(DE3) cells and purified by affinity chromatography using a hexa-histidine tag. 1,6-anhydro-N-acetylmuramic acid (1,6-anhydro-MurNAc) was prepared using reported chemical synthesis methods. Recombinant Rpf protein or 1,6-anhydro-MurNAc were added to R2A cultivation media, and their effect examined on the culturability of bacteria from eight environmental samples including four cockroach guts and four soils. Colony forming units, 16S rRNA gene copies and Illumina amplicon sequencing of the 16S rRNA gene were measured for all eight samples subjected to three different treatments: Rpf, 1,6-anhydro-MurNAc or blank control. Both Rpf and 1,6-anhydro-MurNAc increased the number of colony forming units, and 16S rRNA gene copies across the samples although the protein was more effective. The Rpf and 1,6-anhydro-MurNAc promoted the cultivation of a diverse set of bacteria and specially certain clades of the phyla Actinomycetota and Bacillota. This study opens the path for improved cultivation strategies aiming to isolate and study yet undescribed living bacterial organisms.
Efficacy of Shock Team Implementation for Cardiogenic Shock: A Systematic Review
Authors: Abdelnabi Mohamed , Elsaeidy Ahmed Saad , Aboutaleb Aya Moustafa , Johanis Amit , Ghanem Ahmed K. , Abdelazeem Basel
Published: September 2023

Introduction

Cardiogenic shock (CS) is a critical cardiac condition characterized by low cardiac output leading to end-organ hypoperfusion and associated with high in-hospital mortality rates. It can manifest following acute myocardial infarction or acute exacerbation of chronic heart failure. Despite advancements, mortality rates remain elevated, prompting interest in multidisciplinary approaches to improve outcomes. This manuscript presents a review focused on the concept of a CS team and its potential impact on patient management and outcomes.

Methods

A comprehensive search was performed on March 19th, 2023, covering PubMed, Web of Science, Scopus, Embase, and Cochrane Library. We included primary studies (prospective and retrospective) only and evaluated their quality using the Newcastle-Ottawa Quality Scale. This review was registered in PROSPERO (CRD42023440354).

Results

Six relevant studies with 2066 CS patients were included, of which 1071 were managed by shock teams and 995 received standard care. Findings from the reviewed studies indicated the favorable outcomes associated with implementing CS teams. Patients managed by these teams exhibited higher 30-day and in-hospital survival rates compared to those without team intervention. The implementation of CS teams was linked to reduced in-hospital and ICU mortality rates. Additionally, shock team involvement was associated with shorter door-to-balloon times.

Conclusion

This review highlighted the positive influence of CS teams on patient care, enabling early detection, timely interventions, and shorter ICU stays. Despite implementation challenges, CS teams hold promise for improving management outcomes, necessitating increased attention and ongoing research in multidisciplinary strategies to advance CS care.
Predictors for the Recurrence and Prognosis of Stroke patients within a Multi-Ethnic Asian Population
Authors: Lee Keng Siang , Siow Isabel , Riandini Tessa , Narasimhalu Kaavya , Tan Kelvin Bryan , De Silva Deidre Anne
Published: September 2023

Objective

There is a paucity of studies investigating the risk profile, and outcomes amongst young versus old stroke patients in Asian populations. Singapore is uniquely placed to contribute to the understanding of these risk factors, given our multi-ethnic population. Therefore, the aim of this study was to identify predictors of recurrence and outcome in stroke, comparing the young and the older stroke patients in Singapore.

Methods

This cohort study adhered to STROBE guidelines. Data were obtained from the Singapore Stroke Registry (SSR) from 2005 to 2016, to compare outcomes after first stroke among young (18-49 years) and among old stroke (≥50 years) patients. Outcome measures included recurrent stroke, acute myocardial infarction (AMI) and death from the above. Cox proportional hazards models were performed to determine risk factors for time to each outcome after first stroke, which included demographic and comorbidity variables.

Results

A total of 64,915 patients (6,705 young, and 58,210 old) were included in our analysis. After adjusting for gender, ethnicity, and comorbidities, old stroke patients have a greater hazard for recurrent stroke (HR = 1.20, 95%CI: 1.11-1.29), AMI (HR = 1.72, 95%CI: 1.52-1.94), and for recurrent stroke/AMI (HR = 1.36, 95%CI: 1.27-1.45). The old stroke patients were also more likely to die than younger stroke patients (HR = 2.62, 95%CI: 2.48-2.78). Amongst young stroke patients, males were at greater hazards for recurrent stroke (HR = 1.18, 95%CI: 1.00-1.38), AMI (HR = 1.40, 95%CI: 1.07-1.82), recurrent stroke/AMI (HR = 1.17, 95%CI: 1.02-1.36). However, males were at reduced hazards for death (HR = 0.87, 95%CI: 0.77-0.98). When analysing specifically young stroke patients, compared with the Chinese ethnicity, the Malay ethnicity was predisposed to recurrent stroke (HR = 1.36, 95%CI: 1.14-1.64). Compared with the Chinese ethnicity, both the Malay and Indian ethnicities were predisposed to AMI. The Malay ethnicity was at greater hazards for death (HR = 1.45, 95%CI: 1.27-1.66).

Conclusions

Non-Chinese ethnicities, especially Malay and Indian ethnicities experience poorer outcomes after first stroke. Further optimisation of risk factors targeting these high-priority populations are needed to achieve high quality care.
Efficient ultrasound-mediated drug delivery to orthotopic liver tumors – Direct comparison of doxorubicin-loaded nanobubbles and microbubbles
Authors: Nittayacharn Pinunta , Abenojar Eric , Cooley Michaela , Berg Felipe , Counil Claire , Sojahrood Amin Jafari , Khan Muhammad Saad , Yang Celina , Berndl Elizabeth , Golczak Marcin , Kolios Michael C. , Exner Agata A.
Published: September 2023

Liver metastasis is a major obstacle in treating aggressive cancers, and current therapeutic options often prove insufficient. To overcome these challenges, there has been growing interest in ultrasound-mediated drug delivery using lipid-shelled microbubbles (MBs) and nanobubbles (NBs) as promising strategies for enhancing drug delivery to tumors. Our previous work demonstrated the potential of Doxorubicin-loaded C3F8NBs (hDox-NB, 280 ± 123 nm) in improving cancer treatment in vitro using low-frequency ultrasound. In this study, we investigated the pharmacokinetics and biodistribution of sonicated hDox-NBs in orthotopic rat liver tumors. We compared their delivery and therapeutic efficiency with size-isolated MBs (hDox-MB, 1104 ± 373 nm). Results showed a similar accumulation of hDox in tumors treated with hDox-MBs and unfocused therapeutic ultrasound (hDox-MB+TUS) and hDox-NB+TUS. However, significantly increased apoptotic cell death in the tumor and fewer off-target apoptotic cells in the normal liver were found upon the treatment with hDox-NB+TUS. The tumor-to-liver apoptotic ratio was elevated 9.4-fold following treatment with hDox-NB+TUS compared to hDox-MB+TUS, suggesting that the therapeutic efficacy and specificity are significantly increased when using hDox-NB+TUS. These findings highlight the potential of this approach as a viable treatment modality for liver tumors. By elucidating the behavior of drug-loaded bubblesin vivo, we aim to contribute to developing more effective liver cancer treatments that could ultimately improve patient outcomes and decrease off-target side effects.
Localization of four class I glutaredoxins in the cytosol and the secretory pathway and characterization of their biochemical diversification
Authors: Schlößer Michelle , Moseler Anna , Bodnar Yana , Homagk Maria , Wagner Stephan , Pedroletti Luca , Gellert Manuela , Ugalde José M. , Lillig Christopher H. , Meyer Andreas J.
Published: September 2023

Class I glutaredoxins (GRXs) are catalytically active oxidoreductases and considered key proteins mediating reversible glutathionylation and deglutathionylation of protein thiols during development and stress responses. To narrow in on putative target proteins, it is mandatory to know the subcellular localization of the respective GRXs and to understand their catalytic activities and putative redundancy between isoforms in the same compartment. We show that GRXC1 and GRXC2 are cytosolic proteins with GRXC1 being attached to membranes through myristoylation. GRXC3 and GRXC4 are identified as type II membrane proteins along the early secretory pathway with their enzymatic function on the luminal side. Comparison of all four studied GRXs for their oxidoreductase function highlights biochemical diversification with GRXC1 and GRXC2 being better reductants than GRXC3 and GRXC4 with bis(2-hydroxyethyl) disulfide and oxidized roGFP2 as substrates.Vice versa, GRXC3 and GRXC4 are better oxidants of reduced roGFP2 in the reverse reaction. Analysis of electrostatic surface potentials mirrors the phylogenetic classification of class I GRXs but cannot fully account for the observed kinetic differences in their interaction with roGPF2. Despite localization of two class I GRXs each in the cytosol and the endomembrane system, the respective double null mutants are viable without obvious phenotypes.

Summary statement

We identify Arabidopsis glutaredoxins GRXC3 and GRXC4 as type II membrane proteins in the secretory pathway and GRXC1 as attached to membranes through N-terminal myristoylation. Cytosolic GRXC1 and GRXC2 and luminal GRXC3 and GRXC4 display distinct biochemical properties in their redox activities.
Magnetoelectrics Enables Large Power Delivery to mm-Sized Wireless Bioelectronics
Authors: Kim Wonjune , Tuppen C. Anne , Alrashdan Fatima , Singer Amanda , Weirnick Rachel , Robinson Jacob T.
Published: September 2023

To maximize the capabilities of minimally invasive implantable bioelectronic devices, we must deliver large amounts of power to small implants; however, as devices are made smaller, it becomes more difficult to transfer large amounts of power without a wired connection. Indeed, recent work has explored creative wireless power transfer (WPT) approaches to maximize power density (the amount of power transferred divided by receiver footprint area (length × width)). Here, we analyzed a model for WPT using magnetoelectric (ME) materials that convert an alternating magnetic field into an alternating voltage. With this model, we identify the parameters that impact WPT efficiency and optimize the power density. We find that improvements in adhesion between the laminated ME layers, clamping, and selection of material thicknesses lead to a power density of 3.1 mW/mm2, which is over 4 times larger than previously reported for mm-sized wireless bioelectronic implants at a depth of 1 cm or more in tissue. This improved power density allows us to deliver 31 mW and 56 mW to 10-mm2and 27-mm2ME receivers, respectively. This total power delivery is over 5 times larger than similarly sized bioelectronic devices powered by radiofrequency electromagnetic waves, inductive coupling, ultrasound, light, capacitive coupling, or previously reported magnetoelectrics. This increased power density opens the door to more power-intensive bioelectronic applications that have previously been inaccessible using mm-sized battery-free devices.
Probing the stability and interdomain interactions in the ABC transporter OpuA, using single-molecule optical tweezers
Authors: van der Sleen Lyan , Stevens Jan , Marrink Siewert J. , Poolman Bert , Tych Kasia
Published: September 2023

Transmembrane transporter proteins are essential for the maintenance of cellular homeostasis and, as such, are key drug targets. Many transmembrane transporter proteins are known to undergo large structural rearrangements during their functional cycles. Despite the large amount of detailed structural and functional data available for these systems, our understanding of their dynamics and therefore how they function is generally limited. We introduce an innovative approach which enables us to directly measure the dynamics and stabilities of inter-domain interactions of transmembrane proteins using optical tweezers. Focusing on the osmoregulatory ABC transporter OpuA fromLactococcus lactis, we examine the mechanical properties and potential interactions of its substrate-binding domains. Our measurements are performed in lipid nanodiscs, providing a native-mimicking environment for the transmembrane protein. The technique provides high spatial and temporal resolution and allows us to study the functionally-relevant motions and inter-domain interactions of individual transmembrane transporter proteins in real-time in a lipid bilayer.
A congestion downstream of PSI causes the over-reduction of the electron transport chain inpgr5independent of membrane energization
Authors: Kappel Sandrine , Thiele Wolfram , Gefen-Treves Shany , Henze Anita , Armbruster Ute , Schöttler Mark Aurel
Published: September 2023

The thylakoid protein Proton Gradient Regulation5 (PGR5) is thought to be a key component of cyclic electron flux around photosystem I. Thepgr5mutant is characterized by impaired proton motive force (pmf) formation across the thylakoid membrane, decreased photoprotective non-photochemical quenching (NPQ), and an over-reduction of the PSI acceptor side. This over-reduction has been attributed to impaired photosynthetic control, which down-regulates plastoquinol re-oxidation at the cytochrome b6f complex when the lumen is strongly acidified. Here, using thecgl160ATP synthase assembly mutant, we show that incgl160 pgr5double mutants, both the pmf across the thylakoid membrane and NPQ are fully restored to wild-type levels. However, the acceptor-side limitation of PSI in the double mutants stays comparable to the singlepgr5mutant. This demonstrates that impaired photosynthetic control is not causal for the over-reduction of the PSI acceptor side inpgr5. Instead, we show that both inpgr5and theclg160 pgr5mutants, the entire high-potential chain from cytochrome f to PSI remains strongly reduced in high light. This leads to insufficient oxidizing power for plastoquinol re-oxidation by the cytochrome b6f complex, thus impairing pmf formation. We conclude that PGR5 plays a critical role in electron partitioning downstream of PSI.
Historical causes for the greater proportion of polyploid plants in higher latitudes
Authors: Hagen Eric R. , Vasconcelos Thais , Boyko James D. , Beaulieu Jeremy M.
Published: September 2023

Premise of the Study

The proportion of polyploid plants in a community increases with latitude, and different hypotheses have been proposed about which factors drive this pattern. Here, we aim to understand the historical causes of the latitudinal polyploidy gradient using a combination of ancestral state reconstruction methods. Specifically, we assess whether (1) polyploidization enables movement to higher latitudes (i.e., polyploidization precedes occurrences in higher latitudes) or (2) higher latitudes facilitate polyploidization (i.e., occurrence in higher latitudes precedes polyploidization).

Methods

We reconstruct the ploidy states and ancestral niches of 1,032 angiosperm species at four paleoclimatic time slices ranging from 3.3 million years ago to the present, comprising taxa from four well-represented clades: Onagraceae, Primulaceae,Solanum(Solanaceae), and Pooideae (Poaceae). We use ancestral niche reconstruction models alongside a customized discrete character evolution model to allow reconstruction of states at specific time slices. Patterns of latitudinal movement are reconstructed and compared in relation to inferred ploidy shifts.

Key Results

We find that no single hypothesis applies equally well across all analyzed clades. While significant differences in median latitudinal occurrence were detected in the largest clade, Pooideae, no significant differences were detected in latitudinal movement in any clade.

Conclusions

Our preliminary study is the first to attempt to connect ploidy changes to continuous latitudinal movement, but we cannot favor one hypothesis over another. Given that patterns seem to be clade-specific, a larger number of clades must be analyzed in future studies for generalities to be drawn.
Focused ultrasound ablation of melanoma with boiling histotripsy yields abscopal tumor control and antigen-dependent dendritic cell activation
Authors: Thim Eric A. , Kitelinger Lydia E. , Rivera-Escalera Fátima , Mathew Alexander S. , Elliott Michael R. , Bullock Timothy N. J. , Price Richard J.
Published: September 2023

Background

Boiling histotripsy (BH), a mechanical focused ultrasound ablation strategy, can elicit intriguing signatures of anti-tumor immunity. However, the influence of BH on dendritic cell function is unknown, compromising our ability to optimally combine BH with immunotherapies to control metastatic disease.

Methods

BH was applied using a sparse scan (1 mm spacing between sonications) protocol to B16F10-ZsGreen melanoma in bilateral and unilateral settings. Ipsilateral and contralateral tumor growth was measured. Flow cytometry was used to track ZsGreen antigen and assess how BH drives dendritic cell behavior.

Results

BH monotherapy elicited ipsilateral and abscopal tumor control in this highly aggressive model. Tumor antigen presence in immune cells in the tumor-draining lymph nodes (TDLNs) was ∼3-fold greater at 24h after BH, but this abated by 96h. B cells, macrophages, monocytes, granulocytes, and both conventional dendritic cell subsets (i.e. cDC1s and cDC2s) acquired markedly more antigen with BH. BH drove activation of both cDC subsets, with activation being dependent upon tumor antigen acquisition. Our data also suggest that BH-liberated tumor antigen is complexed with damage-associated molecular patterns (DAMPs) and that cDCs do not traffic to the TDLN with antigen. Rather, they acquire antigen as it flows through afferent lymph vessels into the TDLN.

Conclusion

When applied with a sparse scan protocol, BH monotherapy elicits abscopal melanoma control and shapes dendritic cell function through several previously unappreciated mechanisms. These results offer new insight into how to best combine BH with immunotherapies for the treatment of metastatic melanoma.

Graphical Abstract
Predicting Permeation of Compounds across the Outer Membrane ofP. aeruginosaUsing Molecular Descriptors: Advantages and Limitations
Authors: Manrique P. D. , Leus I. V. , Ĺopez C. A. , Mehla J. , Malloci G. , Gervasoni S. , Vargiu A. V. , Kinthada R. , Herndon L. , Hengartner N. W. , Walker J. K. , Rybenkov V. V. , Ruggerone P. , Zgurskaya H. I. , Gnanakaran S.
Published: September 2023

The ability of Gram-negative pathogens to adapt and protect themselves against antibiotics is a growing threat to public health. The low permeability of the outer membrane (OM) in combination with effective multidrug efflux pumps, constitute the two main antibiotic resistance mechanisms. Though much efforts have been devoted to discover new antibiotics that can bypass these defense mechanisms, no new antibiotic classes have been introduced into clinics in the last 35 years. Models that identify specific descriptors of molecular properties and predict the likelihood that a given compound is capable of successfully permeate the OM and inhibit bacterial growth while avoiding efflux could facilitate the discovery of novel classes of antibiotics. Here we evaluate 174 molecular descriptors of 1260 antimicrobial compounds and study their correlations with antibacterial activity in Gram-negativePseudomonas aeruginosa. While part of these descriptors are computed using traditional approaches based on the physicochemical properties intrinsic to the compounds, ensemble docking and all-atom molecular dynamics (MD) simulations are used to derive additional bacterium-specific mechanistic properties. Descriptors of compound permeation across the OM were calculated using all-atom MD simulations of the compounds in different subregions of the OM model. Descriptors of interactions with efflux pumps were calculated from ensemble docking of compounds targeting specific binding pockets of MexB, the major efflux transporter ofP. aeruginosa. Using these descriptors and the measured antibacterial inhibitory concentrations of compounds, we design and implement a statistical protocol to identify a subset of the molecular properties that are predictive of whether a given compound is a strong or weak permeator across the Gram-negative OM. Our results indicate that 88.4% of the compounds that show measurable antibacterial activity, follow very consistent rules of permeation, which highlight the critical role that the interaction between the compound and the OM have at predicting permeation. The remaining 11.6% of the compounds, although less predictive, are characterized by distinctive structural markers that can be used to minimize classification errors. An implementation of the permeation rules and the structural markers uncovered in our study is shown, and it demonstrates the accuracy of our approach in a set of previously unseen compounds. Taken together, our analysis sheds new light on the key molecular properties that drug candidates should have in order to be effective at OM permeation/inhibition ofP. aeruginosa, and opens the gate to similar data-driven studies in other Gram-negative pathogens.
Ecological feedback limits the spread of an adaptive β-lactamase mutant
Authors: Ruelens Philip , de Ridder Eline , de Visser J. Arjan G.M. , Wortel Meike
Published: September 2023

β-lactamases play an important role in global health problems due to antibiotic resistant bacterial infections. Understanding the spread of these enzymes may inform the development of better drug therapies. However, this is challenging, as β-lactamases affect their own selective advantage through antibiotic degradation, creating complex eco-evolutionary feedback. We investigated the effect of such feedback on the spread of bacterial strains expressing different β-lactamase enzymes conferring varying levels of resistance to the cephalosporin cefotaxime. Specifically, we conducted head-to-head competitions between two related clinically observed β-lactamase mutants, TEM-19 and TEM-52, and varied cefotaxime concentration and cell density to explore the impact of these factors on competitive fitness and coexistence. The results revealed that cell density, which modulates feedback strength, determined whether resistance alleles could replace susceptible alleles or coexist with them. Using a population dynamic model based only on measured parameters, we investigated the underlying mechanisms of these dynamics. By validating our model with experimental data, we show that it can to a large extend predict the equilibrium frequencies based on dose-dependent growth rates and antibiotic degradation activities of the individual strains. Our study emphasizes the importance of considering ecological feedback in the evolution of antibiotic resistance and the potential for predictive modelling, which could be applied in clinical contexts.
Propofol-mediated loss of consciousness disrupts predictive routing and local field phase modulation of neural activity
Authors: Xiong Yihan (Sophy) , Donoghue Jacob A. , Lundqvist Mikael , Mahnke Meredith , Major Alex James , Brown Emery N. , Miller Earl K. , Bastos André M.
Published: September 2023

Predictive coding is a fundamental function of the cortex. The predictive routing model proposes a neurophysiological implementation for predictive coding. Predictions are fed back from deep-layer cortex via alpha/beta (8-30Hz) oscillations. They inhibit the gamma (40-100Hz) and spiking that feed sensory inputs forward. Unpredicted inputs arrive in circuits unprepared by alpha/beta, resulting in enhanced gamma and spiking. To test the predictive routing model and its role in consciousness, we collected data from intracranial recordings of macaque monkeys during passive presentation of auditory oddballs (e.g., AAAAB) before and after propofol-mediated loss of consciousness (LOC). In line with the predictive routing model, alpha/beta oscillations in the awake state served to inhibit the processing of predictable stimuli. Propofol-mediated LOC eliminated alpha/beta modulation by a predictable stimulus in sensory cortex and alpha/beta coherence between sensory and frontal areas. As a result, oddball stimuli evoked enhanced gamma power, late (> 200 ms from stimulus onset) period spiking, and superficial layer sinks in sensory cortex. Therefore, auditory cortex was in a disinhibited state during propofol-mediated LOC. However, despite these enhanced feedforward responses in auditory cortex, there was a loss of differential spiking to oddballs in higher order cortex. This may be a consequence of a loss of within-area and inter-area spike-field coupling in the alpha/beta and gamma frequency bands. These results provide strong constraints for current theories of consciousness.

Significance statement

Neurophysiology studies have found alpha/beta oscillations (8-30Hz), gamma oscillations (40-100Hz), and spiking activity during cognition. Alpha/beta power has an inverse relationship with gamma power/spiking. This inverse relationship suggests that gamma/spiking are under the inhibitory control of alpha/beta. The predictive routing model hypothesizes that alpha/beta oscillations selectively inhibit (and thereby control) cortical activity that is predictable. We tested whether this inhibitory control is a signature of consciousness. We used multi-area neurophysiology recordings in monkeys presented with tone sequences that varied in predictability. We recorded brain activity as the anesthetic propofol was administered to manipulate consciousness. Compared to conscious processing, propofol-mediated unconsciousness disrupted alpha/beta inhibitory control during predictive processing. This led to a disinhibition of gamma/spiking, consistent with the predictive routing model.
Enhancing farmed striped catfish (Pangasianodon hypophthalmus) robustness using dietary β-glucan
Authors: Bano Sheeza , Khan Noor , Fatima Mahroze , Khalique Anjum , Arslan Murat , Nazir Sadia , Asghar Muhammad , Khizar Ayesha , Davies Simon John , Wan Alex H. L.
Published: September 2023

β-glucan is a well-documented feed additive for its potent immunostimulatory properties in many farmed fish species. This study examined how it can also be a promising growth promoter, modulate antioxidant enzyme activities, and act as an anti-stress agent in striped catfish (Pangasianodon hypophthalmus). A 12-week feeding experiment was untaken to determine the effects of dietary β-glucan supplementation at graded levels (0, 0.5, 1.0, and 1.5 g kg-1). Measured indicators suggest that a dietary inclusion level of 1.5 g kg-1β-glucan gave the highest positive responses: weight gain (120.10 g fish-1), survival (98.30 %), and lower FCR (1.70) (P<0.05). Whole body proximate analysis had only revealed that crude protein was significantly affected by the dietary inclusion of β-glucan (P<0.05), with the highest protein content (19.70 %) being in fish that were fed with 1.5 g kg-1β-glucan. Although other inclusion levels (i.e., 0.5 and 1 g kg-1) of β-glucan did not enhance body protein content (P>0.05). The assessment of fatty acid composition in muscle, liver, and adipose tissues showed modifications with the inclusion of β-glucan. Antioxidative-related enzyme activities (inc. catalase, glutathione peroxidase, and superoxide dismutase) that were measured in the liver had higher levels when fed with β-glucan inclusion diets (P<0.05). Following the feed trial, fish were subjected to crowding stress treatment. It was subsequently found that catfish fed with β-glucan-based diet groups had lower levels of blood stress-related indicators compared to the control group with no dietary β-glucan. The use of 1.5 g kg-1of dietary β-glucan resulted in the lowest measured levels of cortisol (43.13 ng mL-1) and glucose (50.16 mg dL-1). This study has demonstrated that the dietary inclusion of β-glucan can have functional benefits beyond the immunological enhancements in striped catfish. Furthermore, its use can increase production levels and mitigate the stress associated with intensive farming practices.
The geometry of low- and high-level perceptual spaces
Authors: Waraich Suniyya A. , Victor Jonathan D.
Published: September 2023

Low-level features are typically continuous (e.g., the gamut between two colors), but semantic information is often categorical (there is no corresponding gradient between dog and turtle) and hierarchical (animals live in land, water, or air). To determine the impact of these differences on cognitive representations, we characterized the geometry of perceptual spaces of five domains: a domain dominated by semantic information (animal names presented as words), a domain dominated by low-level features (colored textures), and three intermediate domains (animal images, lightly-texturized animal images that were easy to recognize, and heavily-texturized animal images that were difficult to recognize). Each domain had 37 stimuli derived from the same animal names. From 13 subjects (9F), we gathered similarity judgments in each domain via an efficient psychophysical ranking paradigm. We then built geometric models of each domain for each subject, in which distances between stimuli accounted for subjects’ similarity judgments and intrinsic uncertainty. Remarkably, the five domains had similar global properties: each required 5 to 7 dimensions, and a modest amount of spherical curvature provided the best fit. However, the arrangement of the stimuli within these embeddings depended on the level of semantic information: dendrograms derived from semantic domains (word, image, and lightly texturized images) were more ‘tree-like’ than those from feature-dominated domains (heavily texturized images and textures). Thus, the perceptual spaces of domains along this feature-dominated to semantic-dominated gradient have a similar global geometry, but the points within the spaces shift to a tree-like organization when semantic information dominates.

Significance Statement

Understanding the nature of knowledge representation is a fundamental goal of systems neuroscience. Low-level visual features (e.g., color), form continuous domains, while semantic information is typically organized into categories and subcategories. Here, using a novel psychophysical paradigm and computational modeling strategy, we find that despite these major differences, the mental representations of these domains lie in spaces with similar overall geometry. However, within these spaces, semantic information is arranged in a more tree-like representation, and the transition to tree-like representations is relatively abrupt once semantic information becomes apparent. These findings provide insight into visual stream processing at an algorithmic level. Furthermore, they support the idea that processing along the ventral stream reflects commonalities of intrinsic cortical function.
Comparative phylogenomic analyses of SNP versus full locus datasets: insights and recommendations for researchers
Authors: Suissa Jacob S. , De La Cerda Gisel Y. , Graber Leland C. , Jelley Chloe , Wickell David , Phillips Heather R. , Grinage Ayress D. , Moreau Corrie S. , Specht Chelsea D. , Doyle Jeff J. , Landis Jacob B.
Published: September 2023

Premise

In phylogenomic analyses, no consensus exists on whether using single nucleotide polymorphisms (SNPs) or including flanking regions (full ‘locus’) is best, nor how strictly missing data should be filtered. Moreover, empirical evidence on whether SNP-only trees are suitable for downstream phylogenetic comparative methods such as divergence time estimation and ancestral state reconstructions is lacking.

Methods

Using GBS data from 22 taxa ofGlycine, we addressed the effects of SNP vs. locus usage and filtering stringency on phylogenomic inference and phylogenetic comparative methods. We compared branch length, node support, and divergence time estimation across eight datasets with varying amounts of missing data and total size.

Results

Our results reveal five aspects of phylogenomic data usage:1. tree topology is largely congruent regardless of data type or filtering parameters;2. filtering missing data too strictly reduces the confidence in some relationships;3. absolute branch lengths vary by two orders of magnitude between datasets;4. data type and branch length variation have little effect on divergence time estimation;5. phylograms significantly alter the estimation of ancestral states.

Discussion

When conducting phylogenomic analyses we recommend not to filter datasets too strictly to minimize the risk of misleading topologies, low support, and inaccurate divergence times.