bluuebunny/crossref_metadata_2025 huggingface dataset:
Perinatal outcomes and genomic characteristics of fetal copy number variants: An individual record linkage study of 713 pregnancies
Authors: Pynaker Cecilia , Norris Fiona , Hui Lisa , Halliday Jane
Published: January 2023

Objective

To determine the perinatal outcomes of fetuses diagnosed with a pathogenic copy number variant (CNV) or variant of uncertain significance (VUS); and to characterize these variants in terms of testing indication, genomic location, size, and inheritance.

Methods

Retrospective study of singleton pregnancies with a pathogenic CNV or VUS from a single laboratory during 2012–2018. Probabilistic record linkage between the prenatal diagnosis dataset and perinatal outcome data for births from 20 weeks gestation was performed. If no birth record was found, this implied a pregnancy loss <20 weeks.

Results

We included 6945 prenatal microarray results; a pathogenic CNV was detected in 230 (3.3%, 95% CI: 2.9%–3.8%) and a VUS in 483 (7.0%, 95% CI: 6.4%–7.6%). Of pregnancies with a pathogenic CNV, 20.0% (95% CI: 15.3%–25.6%) had a live birth, 3.0% (95% CI: 1.5%–6.2%) had a perinatal death (stillbirth or neonatal death), and 77% (95% CI: 71.1%–81.9%) had no birth record. Of those with a VUS, 64.4% (95% CI: 60.0%–68.5%) had a live birth, 1.8% (95% CI: 1.0%–3.5%) had a perinatal death, and no birth record was found for 33.7% (95% CI: 29.7%–38.1%). Most pathogenic CNVs (61.1%) were <7 Mb in size. The most common microdeletion syndromes were DiGeorge, Wolf‐Hirschhorn, and Cri‐du‐chat syndromes.

Conclusion

This study provides an overview of perinatal outcomes and frequency of recurrent CNVs observed in the prenatal microarray era.
Mechanical and surface properties of corona‐treated titanium dioxide‐embedded opaque white low‐density/Linear low‐density polyethylene film
Authors: Das Bidhan , Chakrabarty Debabrata , Mukherjee Avik , Guha Chandan , Bose Saswata
Published: January 2023

This study encompasses the characterization of corona‐treated milky white co‐extruded polyethylene films. The surface energies developed at various applied voltages were investigated by standard wetting (dyne) solutions of binary liquid mixtures. A maximum treatment of 40 dynes/cm was achieved at 3.0 kW of the applied load. Maximum heat seal joint strength of 1.05 kN/m was achieved only when an untreated/untreated surface combination was sealed, while a treated/treated surface combination exhibited the minimum heat seal joint strength of 0.98 kN/m. Standard Scotch tape method was employed for testing peel adhesion. An applied load of more than 3.0 kW shows a decreasing trend in surface energy. The coefficient of friction on the treated surface was also investigated. Aging under different environmental conditions had hardly any impact on the treatment levels within the time period under study. A sufficiently opaque (Opacity—99%) white film at Titanium dioxide (TiO2) loading of 7.5% resulted in a very good barrier film.
Lack of repeatability of radiomic features derived from PET scans: Results from a 18F‐DCFPyL test–retest cohort
Authors: Werner Rudolf A. , Habacha Bilêl , Lütje Susanne , Bundschuh Lena , Kosmala Alekandser , Essler Markus , Derlin Thorsten , Higuchi Takahiro , Lapa Constantin , Buck Andreas K. , Pienta Kenneth J. , Lodge Martin A. , Eisenberger Mario A. , Markowski Mark C. , Pomper Martin G. , Gorin Michael A. , Frey Eric C. , Rowe Steven P. , Bundschuh Ralph A.
Published: January 2023

Objectives

PET‐based radiomic metrics are increasingly utilized as predictive image biomarkers. However, the repeatability of radiomic features on PET has not been assessed in a test–retest setting. The prostate‐specific membrane antigen‐targeted compound 18F‐DCFPyL is a high‐affinity, high‐contrast PET agent that we utilized in a test‐retest cohort of men with metastatic prostate cancer (PC).

Methods

Data of 21 patients enrolled in a prospective clinical trial with histologically proven PC underwent two 18F‐DCFPyL PET scans within 7 days, using identical acquisition and reconstruction parameters. Sites of disease were segmented and a set of 29 different radiomic parameters were assessed on both scans. We determined repeatability of quantification by using Pearson's correlations, within‐subject coefficient of variation (wCOV), and Bland–Altman analysis.

Results

In total, 230 lesions (177 bone, 38 lymph nodes, 15 others) were assessed on both scans. For all investigated radiomic features, a broad range of inter‐scan correlation was found (r, 0.07–0.95), with acceptable reproducibility for entropy and homogeneity (wCOV, 16.0% and 12.7%, respectively). On Bland–Altman analysis, no systematic increase or decrease between the scans was observed for either parameter (±1.96 SD: 1.07/−1.30, 0.23/−0.18, respectively). The remaining 27 tested radiomic metrics, however, achieved unacceptable high wCOV (≥21.7%).

Conclusion

Many common radiomic features derived from a test–retest PET study had poor repeatability. Only Entropy and homogeneity achieved good repeatability, supporting the notion that those image biomarkers may be incorporated in future clinical trials. Those radiomic features based on high frequency aspects of images appear to lack the repeatability on PET to justify further study.
Ligands‐induced open‐close conformational change during DapE catalysis: Insights from molecular dynamics simulations
Authors: Muduli Sunita , Mishra Sabyashachi
Published: January 2023

The microbial enzyme DapE plays a critical role in the lysine biosynthetic pathway and is considered as a potentially safe antibiotic target. In this study, atomistic simulations are employed to identify the modes of essential dynamics that define the conformational response of the enzyme to ligand binding and unbinding. The binding modes and the binding affinities of the products to the DapE enzyme are estimated from the MM‐PBSA method, and the residues contributing to the ligand binding are identified. Various structural analyses and the principal component analysis of the molecular dynamics trajectories reveal that the removal of products from the active site causes a significant change in the overall enzyme structure. Both Cartesian and dihedral principal component analyses are used to characterize the structural changes in terms of domain unfolding and domain twisting motions. In the most dominant mode, that is, the domain unfolding motion, the two catalytic domains move away from the two dimerization domains of the dimeric enzyme, representing a closed‐to‐open conformational change. The conformational changes are initiated by the coordinated movement of three loops (Asp75‐Pro82, Gly240‐Asn244, and Thr347‐Glu353) that trigger a domain‐level movement. From multiple short trajectories, the time constant associated with the domain opening motion is estimated as 43.6 ns. Physiologically, this close‐to‐open conformational change is essential for the regeneration of the initial state of the enzyme for the subsequent cycle of catalytic action and provides the apo enzyme enough flexibility for efficient substrate binding.
Fisetin, a dietary flavonoid, increases the sensitivity of chemoresistant head and neck carcinoma cells to cisplatin possibly through HSP90AA1/IL‐17 pathway
Authors: Ling Junjun , Zhang Liang , Wang Yan , Chang Aoshuang , Huang Yi , Zhao Houyu , Zhuo Xianlu
Published: January 2023

Cisplatin (DDP) resistance is a bottleneck in the treatment of head and neck cancer (HNC), leading to poor prognosis. Fisetin, a dietary flavonoid, has low toxicity and high antitumor activity with unclear mechanisms. We intended to predict the targets of fisetin for reversing DDP‐resistance and further verify their expressions and roles. A network pharmacology approach was applied to explore the target genes. The hub genes were screened out and subjected to molecular docking and experimental verification (in vivo and in vitro). Thirty‐two genes common to fisetin and DDP‐resistance were screened, including three hub genes, namely HSP90AA1, PPIA, and PTPRS. Molecular docking suggested that fisetin and the candidate proteins could bind tightly. HSP90AA1 was identified as the key gene. Administration of fisetin increased the sensitivity of chemoresistant cells (Cal27/DDP and FaDu/DDP) to DDP, accompanied by the downregulation of HSP90AA1 and IL‐17. HSP90AA1 silencing increases the sensitivity of DDP‐resistant cells to DDP, which was mediated by IL‐17. In summary, fisetin might inhibit the chemoresistance of HNC cells to DDP by targeting the HSP90AA1/IL‐17 pathway. Several hub genes might be the targets of fisetin for reversing DDP‐resistance in HNC cells and might also serve as prognostic factors and therapeutic targets for HNC.
Local resilience for low‐carbon transition in Poland: Frameworks, conditions and opportunities for Central European countries
Authors: Verma Pramit , Chodkowska‐Miszczuk Justyna , Lewandowska Agata , Wiśniewski Łukasz
Published: January 2023

Poland, with its objective of switching from a fossil‐fuel base to renewable sources of energy, is a textbook example of an energy transition economy. In this review, the challenges and opportunities for local resilience were identified, followed by an in‐depth analysis of Low Carbon Economy Plans (LCEP) in the 10 largest cities of Poland. The methodology included a bibliometric analysis of the peer‐reviewed studies published from 2010 to 2022, along with K‐means clustering (empirical analysis) of the selected Polish cities. The challenges and opportunities were classified into social (S), economic (E), institutional (I), political (P), technological (T) and environmental (EN) dimensions. Institutional and political dimensions were identified as having a relatively neglected niche in low‐carbon transition research, necessitating an empirical analysis of LCEP at the city scale. Exploiting the knowledge base of traditional sustainable activities, understanding the power relations between the politics, stakeholders and industry elements, and knowledge‐based governance were found vital for creating relevant policies. Three modes of development, multi‐activity goals (MG), energy transition goals (EG), and transport goals (TG) were identified for increasing local resilience. The results illustrate the need to understand low‐carbon policies and their impacts on both energy transitions and local resilience.
Stabilizing High Density Cu Active Sites with ZrO2 Quantum Dots as Chemical Ligand in N‐doped Porous Carbon Nanofibers for Efficient ORR
Authors: Qiao Yue , Zhang Yuanyuan , Xia Shuhui , Wei Chaolong , Chen Yuehui , Chen Shuo , Yan Jianhua
Published: January 2023

The emerging transition metal‐nitrogen‐carbon (MNC) materials are considered as a promising oxygen reduction reaction (ORR) catalyst system to substitute expensive Pt/C catalysts due to their high surface area and potential high catalytic activity. However, MNC catalysts are easy to be attacked by the ORR byproducts that easily lead to the deactivation of metal active sites. Moreover, a high metal loading affects the mass transfer and stability, but a low loading delivers inferior catalytic activity. Here, a new strategy of designing ZrO2 quantum dots and N‐complex as dual chemical ligands in N‐doped bubble‐like porous carbon nanofibers (N‐BPCNFs) to stabilize copper (Cu) by forming CuZrO3‐x/ZrO2 heterostructures and CuN ligands with a high loading of 40.5 wt.% is reported. While the highly porous architecture design of N‐BPCNFs builds a large solidelectrolytegas phase interface and promotes mass transfer. The preliminary results show that the half‐wave potential of the catalyst reaches 0.856 V, and only decreases 0.026 V after 10 000 cycles, exhibiting excellent stability. The proposed strategy of stabilizing metal active sites with both heterostructures and CuN ligands is feasible and scalable for developing high metal loading ORR catalyst.
Trapping Lithium Selenides with Evolving Heterogeneous Interfaces for High‐Power Lithium‐Ion Capacitors
Authors: Tao Shusheng , Momen Roya , Luo Zheng , Zhu Yirong , Xiao Xuhuan , Cao Ziwei , Xiong Dengyi , Deng Wentao , Liu Youcai , Hou Hongshuai , Zou Guoqiang , Ji Xiaobo
Published: January 2023

Transition metal selenides anodes with fast reaction kinetics and high theoretical specific capacity are expected to solve mismatched kinetics between cathode and anode in Li‐ion capacitors. However, transition metal selenides face great challenges in the dissolution and shuttle problem of lithium selenides, which is the same as Li‐Se batteries. Herein, inspired by the density functional theory calculations, heterogeneous can enhance the adsorption of Li2Se relative to single component selenide electrodes, thus inhibiting the dissolution and shuttle effect of Li2Se. A heterostructure material (denoted as CoSe2/SnSe) with the ability to evolve continuously (CoSe2/SnSe→Co/Sn→Co/Li13Sn5) is successfully designed by employing CoSnO3‐MOF as a precursor. Impressively, CoSe2/SnSe heterostructure material delivers the ultrahigh reversible specific capacity of 510 mAh g−1 after 1000 cycles at the high current density of 4 A g−1. In situ XRD reveals the continuous evolution of the interface based on the transformation and alloying reactions during the charging and discharging process. Visualizations of in situ disassembly experiments demonstrate that the continuously evolving interface inhibits the shuttle of Li2Se. This research proposes an innovative approach to inhibit the dissolution and shuttling of discharge intermediates (Li2Se) of metal selenides, which is expected to be applied to metal sulfides or Li‐Se and Li‐S energy storage systems.
Gap height prediction for bolted ring flange connections based on measurements
Authors: Buchholz Aljoscha , Seidel Marc
Published: January 2023

Wind turbine towers and their flange connections are highly fatigue loaded structures. Previous investigations have shown that initial parallel gaps between L‐flange connections, which are resulting from their respective flatness of the contact surfaces, can increase fatigue loads of the connecting fasteners significantly. Flange flatness and/or gap sizes in between flanges must comply with limitations given in relevant standards and therefore must be measured after the manufacturing process and/or during installation. More than 1900 flatness measurements of several offshore wind projects were collected and used to determine initial gaps between flanges analytically. A statistical evaluation allows to determine the distribution of expected gap sizes. The increase of gap height with increasing gap length can be described with linear correlations. Furthermore, the distributions of gap heights are approximated with log‐normal distributions. Parameters for generic log‐normal distributions are derived considering all performed mating simulations. Following the described methodology, gaps can be determined from any large number of flatness measurements. It is proposed to consider the results for flange design.
Game analysis of social capital violations and government regulation in public–private partnership risk sharing
Authors: Li Yan , Wang Xinyu
Published: January 2023

The public–private partnership (PPP) mode entails a variety of risks because the government, private enterprises, financial institutions, and other participants have different interests. To prevent private enterprise violations, dynamic government regulation of PPP risk‐sharing is necessary. Game theory is used here to examine the game behavior of government regulators, private enterprises, intermediary agencies, and the public in the stage of tracking management after the initial risk‐sharing of the project. Primarily, this study analyzes whether private enterprises provide fully compliant reporting and whether government departments check the information by investigating the behavioral motivations behind strategic choices. The primary contribution of this study was to construct a game model of government due diligence inspection under the condition of public participation in regulation. The results of simulations revealed the behavioral characteristics and stability of the participants of PPP in terms of decision‐making. Furthermore, a sensitivity analysis between the state variables and several auxiliary variables was used to reveal the internal relationships of the participants’ strategic choices. This paper offers new insights into reducing violation behavior, protecting the public interest from harm, reducing government departments’ regulatory costs, and promoting effective regulation with public participation.
Dry food affects the oxidative/antioxidant profile of dogs
Authors: Usuga Alexandra , Rojano Benjamín Alberto , Duque Juan Camilo , Mesa Carolina , Restrepo Oliver , Gomez Luis Miguel , Restrepo Giovanni
Published: January 2023

Background

Including adequate concentrations of antioxidants in dog diets has been recommended to reduce their vulnerability to the action of free radicals and reactive oxygen species (ROS). Oxidative stress in dogs has been associated with a wide range of diseases and disorders, as well as with ageing. There are few reports about the influence of diet on dog's antioxidant profile and oxidative stress.

Objective

The objective of this study was to evaluate the effect of four types of dry dog food on the oxidative/antioxidant profile of dogs.

Methods

Six Beagle dog males were used. The study included four experimental diets (dry foods A–D). Each dry food was supplied for 5 weeks to all dogs, for a total of 24 weeks, including an adaptation week between one food and another. For each dry dog food, the total phenolic content (TPC), total antioxidant capacity (TAC) and cytotoxicity were evaluated. Each week, a blood sample was collected to measure ROS and TAC of plasma. A crossover repeated measures design was used. Mixed models were adjusted, and means were compared using the Tukey test.

Results

Food A had the highest values for TPC and TAC. Food C had the lowest levels of ROS, whereas food B had the highest TAC in the blood plasma. The dog had a significant influence on the redox state of its blood plasma, even when the same dog was fed the different dry foods.

Conclusion

Dry dog food influences the oxidative/antioxidant profile of dog's blood plasma; however, this seems to be unrelated to the antioxidant profile of the food.
Operational islands and black hole dissipation in JT gravity
Authors: De Vuyst Julian , Mertens Thomas G.
Published: January 2023

Abstract

In this work, we revisit the problem of finding entanglement islands in 2d Jackiw-Teitelboim (JT) gravity. We implement the following adjustments to the traditional setup: (1) we do not explicitly couple to a non-gravitating system, instead we implement only pure absorption into a fiducial detector, (2) we utilise the operationally defined renormalised matter entanglement entropy, as defined by the boundary observer’s wordline. We show that this leads to a unitary Page curve that we explicitly compute, with an island outside of the event horizon. Next, we extend the analysis to a charged and/or supersymmetric black hole. We find that in a certain regime the charged black hole grows first as it emits superradiation before eventually dissipating. We obtain similar results when embedding the system in a supersymmetric setting.
Flavor structures of quarks and leptons from flipped SU(5) GUT with A4 modular flavor symmetry
Authors: Du Xiao Kang , Wang Fei
Published: January 2023

Abstract

We propose to generate the flavor structures of the Standard Model plus neutrinos from flipped SU(5) GUT with A4 modular flavor symmetry. Possible way to assign different moduli values for quarks and leptons in modular GUT scheme is discussed. We propose to reduce the multiple modular symmetries to a single modular symmetry in the low energy effective theory with proper boundary conditions. We classify all possible scenarios in this scheme according to the assignments of the modular A4 representations for matter superfields and give the expressions of the quark and lepton mass matrices predicted by our scheme at the GUT scale. After properly selecting the modular weights for various superfields that can lead to better fitting, we can obtain the best-fit points with the corresponding χ2 values for the sample subscenarios. We find that the flavor structures of the Standard Model plus neutrinos can be fitted perfectly in such a A4 modular flavor GUT scheme with single or two modulus fields. Especially, the $$ {\chi}_{\textrm{total}}^2 $$

χ
total
2

of our fitting can be as low as 1.558 for sample IX′ of scenario III even if only a single common modulus field for both quark and lepton sectors is adopted. The most predictive scenario III, in which all superfields transform as triplets of A4, can be fitted much better with two independent moduli fields τq, τl for quark sector and lepton sector ($$ {\chi}_{\textrm{total}}^2 $$

χ
total
2

≈ 95) than that with the single modulus case ($$ {\chi}_{\textrm{total}}^2 $$

χ
total
2

≈ 282.4).
Chiral higher-spin holography in flat space: the Flato-Fronsdal theorem and lower-point functions
Authors: Ponomarev Dmitry
Published: January 2023

Abstract

We prove the flat space analogue of the Flato-Fronsdal theorem. It features the flat space singleton representation suggested recently. We do that by deriving a kernel that intertwines a pair of singleton representations with massless higher-spin fields in flat space. Next, we derive two-point functions of flat space singletons, which are then used to construct two- and three-point scattering amplitudes in the dual theory of massless higher-spin fields. These amplitudes agree with amplitudes in the chiral higher-spin theory.
Analytic treatment of 3-flavor neutrino oscillation and decay in matter
Authors: Chattopadhyay Dibya S. , Chakraborty Kaustav , Dighe Amol , Goswami Srubabati
Published: January 2023

Abstract

We present compact analytic expressions for 3-flavor neutrino oscillation probabilities with invisible neutrino decay, where matter effects have been explicitly included. We take into account the possibility that the oscillation and decay components of the effective Hamiltonian do not commute. This is achieved by employing the techniques of inverse Baker-Campbell-Hausdorff (BCH) expansion and the Cayley-Hamilton theorem applied in the 3-flavor framework. If only the vacuum mass eigenstate ν3 decays, we show that the treatment of neutrino propagation may be reduced to an effective 2-flavor analysis in the One Mass Scale Dominance (OMSD) approximation. The oscillation probabilities for Pμμ, Pee, Peμ and Pμe — relevant for reactor, long baseline and atmospheric neutrino experiments — are obtained as perturbative expansions for the case of only ν3 decay, as well as for the more general scenario where all components of the decay matrix are non-zero. The analytic results thus obtained match the exact numerical results for constant density matter to a high precision and provide physical insights into possible effects of the decay of neutrinos as they propagate through Earth matter. We find that the effects of neutrino decay are most likely to be observable in Pμμ. We also point out that at any long baseline, the oscillation dips in Pμμ can show higher survival probabilities in the case with decay than without decay, and explain this feature using our analytic approximations.
Blackbox: Psychosoziale Fälle in der Notaufnahme
Authors: Ruegenberg Alina , Schmiedhofer Martina , Kreutzberg Anika , Henschke Cornelia , Möckel Martin , Slagman Anna
Published: January 2023

Ziel der Studie

Ziel der Studie ist a) die Prävalenzerfassung psychosozialer Notfälle in der Notaufnahme, b) die Ermittlung des Anteils der nicht als (Neben‑)Diagnose kodierten psychosozialen Fälle (Dunkelziffer) und c) die Charakterisierung identifizierter Patient*innen.

Methodik

In einer retrospektiven Studie wurden psychosoziale Notfälle einer Kalenderwoche aus der Routinedokumentation der zentralen Notaufnahme (ZNA) der Charité – Universitätsmedizin Berlin, Charité Campus Mitte (CCM) identifiziert. Nach Ausschluss von geplant aufgenommenen Fällen wurden 862 Patient*innen in die Studie eingeschlossen. Die identifizierten psychosozialen Notfälle wurden hinsichtlich ihrer soziodemografischen und klinischen Merkmale deskriptiv analysiert und mit anderen Notfällen verglichen.

Ergebnisse

Die Prävalenz psychosozialer Notfälle unter Notaufnahmepatient*innen im angegebenen Zeitraum betrug 11,9 % (n = 103). Ein Großteil der psychosozialen Notfälle war in den Diagnosen nicht (35,9 %) oder nicht vollständig (20,4 %) kodiert. Es gab einen statistisch relevanten Unterschied in der Geschlechterverteilung mit einem signifikant höheren Männeranteil unter den psychosozialen Notfällen (70,9 %) im Vergleich zu anderen Notfällen (50,7 %; p < 0,0001). Die 2 häufigsten Behandlungsanlässe unter den psychosozialen Notfällen waren Substanzmissbrauch (66,0 %) und Obdachlosigkeit (20,4 %).

Schlussfolgerungen

Diese Studie zeigt einen relevanten Anteil an in den Routinedaten dokumentierten psychosozialen Behandlungsanlässen an allen Behandlungsanlässen in der Notaufnahme und einen hohen Anteil von in den kodierten Diagnosen nicht erfassten Fällen (Dunkelziffer) auf. Notaufnahmen stellen somit eine wichtige Anlaufstelle für vulnerable Patient*innengruppen dar, die dort bisher nicht ausreichend identifiziert werden.
Sex-differences in anxiety, neuroinflammatory markers, and enhanced fear learning following chronic heroin withdrawal
Authors: Parekh Shveta V. , Adams Lydia O. , Barkell Gillian A. , Lysle Donald T.
Published: January 2023

Post-traumatic stress disorder (PTSD) and opioid use disorder (OUD) are comorbid in clinical populations. However, both pre-clinical and clinical studies of these co-occurring disorders have disproportionately represented male subjects, limiting the applicability of these findings. Our previous work has identified chronic escalating heroin administration and withdrawal can produce enhanced fear learning. This behavior is associated with an increase in dorsal hippocampal (DH) interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and glial fibrillary acidic protein (GFAP) immunoreactivity. Further, we have shown that these increases in IL-1β and TNF-α are mechanistically necessary for the development of enhanced fear learning. Although these are exciting findings, this paradigm has only been studied in males. The current studies aim to examine sex differences in the behavioral and neuroimmune effects of chronic heroin withdrawal and future enhanced fear learning. In turn, we determined that chronic escalating heroin administration can produce withdrawal in female rats comparable to male rats. Subsequently, we examined the consequence of heroin withdrawal on future enhanced fear learning and IL-1β, TNF-α, and GFAP immunoreactivity. Strikingly, we identified sex differences in these neuroimmune measures, as chronic heroin administration and withdrawal does not produce enhanced fear learning or immunoreactivity changes in females. Moreover, we determined whether heroin withdrawal produces short-term and long-term anxiety behaviors in both female and males. Collectively, these novel experiments are the first to test whether heroin withdrawal can sensitize future fear learning, produce neurobiological changes, and cause short-term and long-term anxiety behaviors in female rats.
A V–Y fasciocutaneous flap for perineal reconstruction following abdominoperineal resection: quicker and better than a myocutaneous gluteal flap?
Authors: Gertler Joshua N. , Sommar Pehr , Lindqvist Ebba K.
Published: January 2023

Background

Abdominoperineal resection in patients with anorectal malignancies may require flap reconstruction for large perineal defects as an adjunct to the oncologic surgery. Perineal reconstruction should be timely, safe, and yield good long-term functional results. There is no agreement on the ideal approach.

Methods

We performed a retrospective observational cohort study to compare clinical outcomes and post-operative complications between a musculocutaneous gluteal flap and a fasciocutaneous V–Y flap for perineal reconstruction. We included all patients who underwent abdominoperineal resection at Karolinska University Hospital between 2016 and 2019. Patient demographics and comorbidities, as well as treatment data, post-operative complications, and follow-up data, were collected from medical records.

Results

A total of 44 patients were included with a mean age of 65 years where 73% were men. Reconstruction was made with a musculocutaneous gluteal flap in 19 patients (43%) and with a fasciocutaneous V–Y flap in 25 patients (57%). Flap-related post-operative complications occurred in 39% of the patients and the incidence did not differ between the groups (p = 0.831). Neither operative time, time to ambulant mobility, time to drain removal, nor time to epidural removal differed between the groups (p > 0.05). Four patients in the gluteal flap group and one patient in the V–Y flap group presented with long-term complications.

Conclusions

Post-operative complications are common after perineal reconstruction following abdominoperineal resection regardless of reconstructive approach. Our study confirms that both a fasciocutaneous and a musculocutaneous flap are acceptable options for perineal reconstruction.

Level of evidence: Level III, risk/prognostic study.
Impact of the Intermittent Pringle Maneuver for Predicting Post‐hepatectomy Liver Failure: A Cohort Study of 597 Consecutive Patients
Authors: Morino Koshiro , Seo Satoru , Yoh Tomoaki , Toda Rei , Yoshino Kenji , Nishio Takahiro , Yamamoto Gen , Ishii Takamichi , Taura Kojiro , Hatano Etsuro
Published: January 2023

Background

Intermittent Pringle maneuver (PM) is widely performed to reduce blood loss during hepatectomy; however, its impact on clinically relevant post‐hepatectomy liver failure (PHLF) remains controversial. This study aimed to assess the impact of PM on PHLF and explore whether PM provides additional value for predicting PHLF.

Methods

Consecutive patients, who underwent hepatectomy without biliary and/or vascular reconstruction between 2011 and 2018 in a single institution, were retrospectively analyzed. The main outcome was PHLF grades B/C as defined by the International Study Group of Liver Surgery. A multivariable logistic regression model of variables significantly associated with PHLF was established. The model's predictive ability was assessed by the area under the receiver operating characteristic curve (AUROC).

Results

Among 597 patients, PHLF occurred in 42 (7.0%). PM was applied in 421 patients (70.5%) and was associated with the development of PHLF (PM vs. no‐PM: 9.7 vs. 0.6%, P < 0.001). After the propensity score matching, patients with PM experienced significantly increased rates of PHLF (P = 0.010). Rem‐ALPlat index (including future liver remnant, preoperative albumin level, and platelet count; P < 0.001), the number of PMs (P = 0.032), and blood loss (P = 0.007) were identified as significant predictors of PHLF. The model's AUROC combined with the intraoperative variables was higher than that of the preoperative model alone (0.877 vs. 0.789, P = 0.004).

Conclusions

PM was involved in the occurrence of clinically relevant PHLF. Further, intraoperative factors including PM may provide additional value to predict PHLF and may facilitate early post‐hepatectomy intervention.
B3-Läsionen der Mamma: Histologische, klinische und epidemiologische Aspekte
Authors: Varga Zsuzsanna , Sinn Peter , Lebeau Annette
Published: January 2023

B3-Läsionen der Mamma stellen eine heterogene Gruppe von Läsionen mit unsicherem Malignitätspotenzial dar, welche histologisch klar definierte Diagnosen beinhalten und welche in diagnostischem und therapeutischem Kontext unterschiedlich gewichtet und behandelt werden. Vor allem die Entscheidung über die Schritte nach der Diagnose einer B3-Läsion an Stanzbiopsie oder Vakuumbiopsie können eine Herausforderung darstellen. B3-Läsionen werden oft wegen bildgebenden Kalzifikationen oder Herdbefunden entdeckt und biopsiert. Histologisch können die Veränderungen einer Reihe von häufigen Diagnosen (wie die atypische duktale Hyperplasie, die klassische lobuläre Neoplasie, flache Epithelatypien, intraduktale Papillome, radiäre Narben oder fibroepitheliale Tumoren vom Typ eines Phylloidestumors) oder seltenen Diagnosen (wie Mukozelen-ähnliche Läsion, atypische apokrine Läsionen und seltene stromale Proliferate) zugeordnet werden. Immunhistochemie ist hilfreich in der Differenzierung und einer korrekten nomenklatorischen Zuordnung dieser Läsionen (vor allem Östrogenrezeptoren, basale Zytokeratine, Myoepithelmarker oder stromale Markerpanel). Im klinischen Kontext bleibt die Korrelation der bildgebenden und histologischen Befunde der wichtigste Faktor in der Entscheidung der nächsten diagnostischen/therapeutischen Schritte.
Hospital rating websites play a minor role for uro-oncologic patients when choosing a hospital for major surgery: results of the German multicenter NAVIGATOR-study
Authors: Groeben Christer , Boehm Katharina , Koch Rainer , Sonntag Ulrich , Nestler Tim , Struck Julian , Heck Matthias , Baunacke Martin , Uhlig Annemarie , Koelker Mara , Meyer Christian P. , Becker Benedikt , Salem Johannes , Huber Johannes , Leitsmann Marianne
Published: January 2023

Purpose

Hospital rating websites (HRW) offer decision support in hospital choice for patients. To investigate the impact of HRWs of uro-oncological patients undergoing elective surgery in Germany.

Methods

From 01/2020 to 04/2021, patients admitted for radical prostatectomy, radical cystectomy, or renal tumor surgery received a questionnaire on decision-making in hospital choice and the use of HRWs at 10 German urologic clinics.

Results

Our study includes n = 812 completed questionnaires (response rate 81.2%). The mean age was 65.2 ± 10.2 years; 16.5% were women. Patients were scheduled for prostatectomy in 49.1%, renal tumor surgery in 20.3%, and cystectomy in 13.5% (other 17.1%). Following sources of information influenced the decision process of hospital choice: urologists’ recommendation (52.6%), previous experience in the hospital (20.3%), recommendations from social environment (17.6%), the hospital's website (10.8%) and 8.2% used other sources. Only 4.3% (n = 35) used a HRW for decision making. However, 29% changed their hospital choice due to the information provided HRW. The most frequently used platforms were Weisse-Liste.de (32%), the AOK-Krankenhausnavigator (13%) and Qualitaetskliniken.de (8%). On average, patients rated positively concerning satisfaction with the respective HRW on the Acceptability E-Scale (mean values of the individual items: 1.8–2.1).

Conclusion

In Germany, HRWs play a minor role for uro-oncologic patients undergoing elective surgery. Instead, personal consultation of the treating urologist seems to be far more important. Although patients predominantly rated the provided information of the HRW as positive, only a quarter of users changed the initial choice of hospital.
Concepts of association between cancer and ionising radiation: accounting for specific biological mechanisms
Authors: Eidemüller Markus , Becker Janine , Kaiser Jan Christian , Ulanowski Alexander , Apostoaei A. Iulian , Hoffman F. Owen
Published: January 2023

The probability that an observed cancer was caused by radiation exposure is usually estimated using cancer rates and risk models from radioepidemiological cohorts and is called assigned share (AS). This definition implicitly assumes that an ongoing carcinogenic process is unaffected by the studied radiation exposure. However, there is strong evidence that radiation can also accelerate an existing clonal development towards cancer. In this work, we define different association measures that an observed cancer was newly induced, accelerated, or retarded. The measures were quantified exemplarily by Monte Carlo simulations that track the development of individual cells. Three biologically based two-stage clonal expansion (TSCE) models were applied. In the first model, radiation initiates cancer development, while in the other two, radiation has a promoting effect, i.e. radiation accelerates the clonal expansion of pre-cancerous cells. The parameters of the TSCE models were derived from breast cancer data from the atomic bomb survivors of Hiroshima and Nagasaki. For exposure at age 30, all three models resulted in similar estimates of AS at age 60. For the initiation model, estimates of association were nearly identical to AS. However, for the promotion models, the cancerous clonal development was frequently accelerated towards younger ages, resulting in associations substantially higher than AS. This work shows that the association between a given cancer and exposure in an affected person depends on the underlying biological mechanism and can be substantially larger than the AS derived from classic radioepidemiology.
Frailty as a predictor of mortality and readmission rate in secondary mitral regurgitation
Authors: Uzel Robert , Rezar Richard , Bruno Raphael Romano , Wernly Sarah , Jung Christian , Delle Karth Georg , Datz Christian , Hoppichler Friedrich , Wernly Bernhard
Published: January 2023

Introduction

Selection in patients with functional mitral regurgitation (MR) to identify responders to interventions is challenging. In these patients, frailty might be used as a multidimensional parameter to summarize the resilience to stressors. Our objective was to evaluate frailty as a predictor of outcome in patients with moderate to severe secondary MR.

Methods

We conducted a single-center retrospective observational cohort study and included 239 patients with moderate to severe secondary MR aged 65 years or older between 2014 and 2020. Echocardiography was performed at baseline; frailty was evaluated using the clinical frailty scale (CFS). The combined primary endpoint was hospitalization for heart failure and all-cause mortality.

Results

A total of 53% (127) of all patients were classified as CFS 4 (living with mild frailty) or higher. Frail patients had a higher risk for the combined endpoint (hazard ratio, HR 3.70, 95% confidence interval, CI 2.12–6.47; p < 0.001), 1‑year mortality (HR 5.94, 95% CI 1.76–20.08; p < 0.001) even after adjustment for EuroSCORE2. The CFS was predictive for the combined endpoint (AUC 0.69, 95% CI 0.62–0.75) and outperformed EuroSCORE2 (AUC 0.54, 95% CI 0.46–0.62; p = 0.01). In sensitivity analyses, we found that frailty was associated with adverse outcomes at least in trend in all subgroups.

Conclusion

For older, medically treated patients with moderate to severe secondary mitral regurgitation, frailty is an independent predictor for the occurrence of death and heart failure-related readmission within 1 year and outperformed the EuroSCORE2. Frailty should be assessed routinely in patients with heart failure to guide clinical decision making for mitral valve interventions or conservative treatment.
Current status and molecular epidemiology of rabies virus from different hosts and regions in Malawi
Authors: Kainga Henson , Chatanga Elisha , Phonera Marvin Collen , Kothowa John Pilate , Dzimbiri Precious , Kamwendo Gladson , Mulavu Malala , Khumalo Cynthia Sipho , Changula Katendi , Chambaro Herman , Harima Hayato , Kajihara Masahiro , Mkandawire Kholiwe , Chikungwa Patrick , Chulu Julius , Njunga Gilson , Chitanga Simbarashe , Mubemba Benjamin , Sasaki Michihito , Orba Yasuko , Qiu Yongjin , Yamagishi Junya , Simulundu Edgar , Takada Ayato , Namangala Boniface , Sawa Hirofumi , Muleya Walter
Published: January 2023

Although rabies is endemic in Malawi, there have been no studies in which rabies virus was systematically investigated and characterized in multiple animal hosts in that country. In order to provide molecular epidemiological data on rabies virus in Malawi, 683 suspected rabies case reports from 2008 to 2021 were examined, and 46 (dog = 40, cow = 5, and cat = 1) viable rabies-positive brain samples archived at the Central Veterinary Laboratory (CVL), Lilongwe, Malawi, were analyzed genetically. The results showed an increase in the submission of brain samples from 2008 to 2010, with the highest number of submissions observed in 2020. Of the 683 case reports analyzed for the period under review, 38.1% (260/683) (CI: 34.44 – 41.84) were confirmed by direct fluorescent antibody test. Among the confirmed cases, 65.4% (170/260) (CI: 59.23 – 71.09) were canine rabies. Further, phylogenetic analysis revealed that sequences from different animal hosts clustered together within the Africa 1b lineage, suggesting that the strains circulating in livestock are similar to those in domestic dogs. This finding supports the hypothesis that canine rabies is spilling over to livestock and emphasizes the need for further studies to provide data for effective control of rabies in Malawi.
Endorsement of a single-item measure of sleep disturbance during pregnancy and risk for postpartum depression: a retrospective cohort study
Authors: Felder Jennifer N. , Roubinov Danielle , Zhang Li , Gray Mark , Beck Arne
Published: January 2023

Poor prenatal sleep quality is associated with increased risk for depressive symptoms but may go undetected in brief, busy prenatal care visits. Among non-depressed pregnant participants, we evaluated whether 1) the endorsement of sleep disturbance on a depression questionnaire predicted postpartum depressive symptoms, 2) the strength of these associations was higher than other somatic symptoms of pregnancy and depression (i.e., fatigue, appetite disturbance), and 3) the endorsement of prenatal sleep disturbance varied by participant characteristics. In this retrospective cohort study, participants had a live birth and completed Patient Health Questionnaire (PHQ-9) during pregnancy and within 8 weeks postpartum between 2012 and 2017. Participants who were non-depressed during pregnancy (PHQ-9 < 10) were included (n = 3619). We operationalized sleep disturbance, fatigue, and appetite disturbance as endorsement of item 3, 4, and 5 on the PHQ-9, respectively, and postpartum depressive symptoms as PHQ-9 total score ≥ 10. Participant characteristic variables included age, race, ethnicity, parity, gestational age at delivery, and preterm birth. Prenatal sleep disturbance was associated with higher odds of postpartum depressive symptoms (aORs 1.9, 95% CI 1.2–3.1 for first trimester; 3.7, 95% CI 1.5–11.5 for second trimester; 3.4, 95% CI 1.9–6.8 for third trimester). Fatigue and appetite disturbance in the first and third trimesters were associated with higher odds of postpartum depressive symptoms. Sleep disturbance varied by race during the first and second trimesters (p < 0.05) and was highest among Black or African American participants (61.8–65.1%). A routinely administered single-item measure of sleep disturbance could identify otherwise lower-risk pregnant individuals who may benefit from depression prevention efforts.
Photobiomodulation for Alzheimer’s disease: photoelectric coupling effect on attenuating Aβ neurotoxicity
Authors: Tian Zixi , Wang Panpan , Huang Kai , Yu Jie , Zhang Mange , Liu Yanming , Zhao Hang , Zhu Beilei , Huang Xuerong , Tong Zhiqian
Published: January 2023

Alzheimer’s disease (AD) and dementia are the most worrying health problems faced by people globally today. Although the pathological features of AD consisting of amyloid-beta (Aβ) plaques in the extracellular space (ECS) and intracellular tau tangles are well established, the developed medicines targeting these two proteins have not obtained the expected clinical effects. Photobiomodulation (PBM) describes the therapeutic use of red light (RL) or near-infrared light (NIR) to serve as a noninvasive neuroprotective strategy for brain diseases. The present review discusses the mechanisms of the photoelectric coupling effect (light energy-induced special electronic transition-related alterations in protein structure) of PBM on reducing Aβ toxicity. On the one hand, RL or NIR can directly disassemble Aβ in vitro and in vivo. On the other hand, formaldehyde (FA)-inhibited catalase (CAT) and H2O2-inactived formaldehyde dehydrogenase (FDH) are formed a vicious circle in AD; however, light energy not only activates FDH to degrade excessive FA (which crosslinks Aβ monomer to form Aβ oligomers and senile plaques) but also sensitizes CAT to reduce hydrogen peroxide levels (H2O2, which can facilitate Aβ aggregation and enhance FA generation). In addition, it also activates mitochondrial cytochrome-c to produce ATP in the neurons. Clinical trials of phototherapeutics or oral coenzyme Q10 have shown positive effects in AD patients. Hence, a promising strategy combined PBM with nanopacked Q10 has been proposed to apply for treating AD.
Assessing feral swine damage in the western gulf region of Arkansas, Louisiana, and Texas
Authors: Tian Nana , Gan Jianbang , Holley Gordon
Published: January 2023

Feral swine (Sus scrofa) as an invasive species in the U.S. have caused severe damage to natural resources through competing for food resources with domestic livestock and destroying habitat by rooting and wallowing. Given their increased population and wide distribution in the southern U.S., feral swine control is becoming an urgent issue for both natural resource managers and landowners. We conducted a three-state mail survey to examine feral swine damage in Arkansas, Louisiana, and East Texas in the western gulf region in 2021. Our results reveal that feral swine activities like rooting and wallowing can cause severe and widespread damage to agriculture and forestry. Among the most reported and concerned damage by feral swine were crops, pastures, livestock, and loss of land value. Soybean damage was the most important agricultural crop damage in both Arkansas and Louisiana while it was hay, silage, and forage crops in East Texas. In terms of livestock damage, beef cattle and calves were the most common and severe damage in all three states. Average economic loss due to feral swine damage was estimated at $67.13/ha, $42.96/ha, $27.31/ha, and $57.54/ha for landowners in the region who owned cropland, forestland, pastureland, and multiple land types, respectively. Those findings could help both landowners and wildlife management personnel understand the negative societal impact of feral swine, and they could also facilitate the comparison between expected benefits and costs of control programs/options for feral swine in the southern states.
An Asymptotic Theory for the Flow over Heterogeneous Roughness
Authors: Segalini Antonio , Janzon Erik
Published: January 2023

The flow over arbitrary roughness changes is investigated, revisiting the analysis of Belcher et al. (Q J R Meteorol Soc 116:611–635, 1990) regarding surface-roughness heterogeneity. The proposed theory is restricted to steady neutral boundary layers over flat regions with changes of roughness sufficiently slow and mild to inhibit the growth of nonlinear terms. The approach is based on a triple-deck decomposition of the flow above the roughness, although only the first two layers are interactive at leading order. Two experimental datasets (one with a smooth-to-rough and the other with a rough-to-smooth transition) are used to validate the theory. The latter is further compared against two large-eddy simulations featuring chessboard patterns of alternating surface roughness with relatively short and long length scales, respectively. All the comparisons show that the proposed theory is able to reasonably assess the wind-field perturbation due to the roughness heterogeneity, supporting the use of the model to quickly assess the effect of roughness changes in the flow field.