bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthetic Approaches towards Peptide‐Conjugates of Pt(II) Compounds with an (O,S) Chelating Moiety
Authors: Mügge Carolin , Nowak Nora , Strack Martin , Metzler‐Nolte Nils , Weigand Wolfgang
Published: October 2023

Metal‐containing peptide (bio−)conjugates have received continuous interest due to their enormous potential for bioinorganic and medicinal research. In many bioconjugates the chemical inertness of the metal‐containing units facilitates synthesis e. g. by copper‐catalyzed alkyne−azide cycloaddition or the formation of peptide bonds. However, when the metal complex contains labile ligands, which are often critical to their biological activity, the synthetic proceeding requires careful planning. Here, we report on the synthesis of a set of peptide bioconjugates with a platinum(II) core, coordinated through widely variable (O,S) chelating β‐hydroxydithiocinnamic ester and two monodentate ligands. We have evaluated the synthetic applicability of metal−peptide bioconjugation techniques between the model peptide Leu5−enkephalin and differently functionalized (O,S)Pt units. Within this, the type and position of anchor used at the β‐hydroxydithiocinnamic unit proved to be crucial for success, but equally important was the synthetic order of conjugation and complexation. In this work, synthetic approaches for the linkage of metal complexes that are coordinated by functionalized ligands towards peptides were explored. Two general methods to link the studied (O,S)Pt pharmacophore to the model peptide, Leu5−enkephalin, have been applied, namely the most prominent “click” reaction, CuAAC, and the linking via amide bonds. Overall, it could be shown that the structural motif of the (O,S)Pt compounds presented here offers multiple possibilities of derivatization, so that bioconjugation towards peptides can be made possible. Depending on the demands made on the resulting metal bioconjugate, both the dithioester and the aromatic unit of β‐hydroxydithiocinnamic esters can be used as anchor for peptides. However, from our results here, it can be concluded that anchoring at the aromatic subsite seems preferable from a synthetic point of view as the spatial distance of the reactive terminal functional group (alkyne or azide) to the metal center may avoid intramolecular reactions. Also, for using azide−alkyne click chemistry as a conjugation strategy, the (O,S) unit should contain the azide function and not the alkyne function, as triple bond hydration may occur. Classical amide‐bond conjugation also proved to be a suitable method in our hands when performed in solution. A coupling of the β‐hydroxydithiocinnamic unit to resin‐bound peptide would not be possible due to the typically harsh cleavage conditions.
Experimental determination of the discharge flow coefficient at a doorway for fire induced flow in natural and mixed convection
Authors: Koched A. , Pretrel H. , Vauquelin O. , Audouin L.
Published: October 2023

The study is an experimental investigation of the discharge flow coefficient at a doorway‐type opening in the case of a fire in an enclosure open to atmosphere. Natural and mixed convection flows are considered with the use of mechanical ventilation. The discharge coefficient is defined as the ratio between the effective flow rate determined experimentally and a theoretical flow rate based on a Bernoulli approach. The effective mass flow rate is obtained from velocity field measured with stereoscopic particle image velocimetry technique. The theoretical flow rate is calculated from vertical temperature profiles measured from both sides of the doorway. Only inflow rate is considered for the calculation of the discharge coefficient. In natural convection mode, a CD value of 0.54 ± 0.5 is obtained on a reduced‐scale opening (to be compared with 0.68 at large scale). In a mixed convection case, the discharge coefficient is much lower and reaches 0.26 ± 0.06. This study shows that the discharge coefficient CD may vary significantly regarding the dimension of the opening and the flow conditions (natural and mixed convection). It illustrates the limits of considering a constant discharge coefficient when dealing with doorway flows in a confined and mechanically ventilated compartment. Copyright © 2014 John Wiley & Sons, Ltd.
Use of different food additives to control browning in fresh‐cut potatoes
Authors: Li Guoqin , Wang Xinxin , Zhu Hongmei , Li Guifeng , Du Junjie , Song Xiaoqing , Erihemu
Published: October 2023

Fresh‐cut potato browning is a severe problem in the potato processing industry. Ascorbic acid, L‐cysteine, hydrogen sulfide (H2S), and nitric oxide (NO) have been reported to reduce the browning in fresh‐cut vegetables and fruits. We compared the effect of each food additive at its commonly used concentration on fresh‐cut potato browning in order to choose a highly efficient treatment and explore its mechanism. Fresh‐cut potato slices were immersed in 0.3 mmol L−1 ascorbic acid, 0.7 mmol L−1 L‐cysteine, 0.7 mmol L−1 H2S, or 2.0 mmol L−1 NO for 10 min and stored at 4°C until the measurements finished. Results showed that the ascorbic acid and L‐cysteine treatments showed less browning than the control treatment, while the H2S and NO treatments did not. Ascorbic acid increased total phenolic content, polyphenol oxidase (PPO) and peroxidase (POD) activities, while L‐cysteine decreased PPO and POD activities with no change in total phenolic content. In addition, these two treatments did not influence respiration rate, weight loss, or rot index. In conclusion, ascorbic acid (0.3 mmol L−1) and L‐cysteine (0.7 mmol L−1) can be valuable means to control fresh‐cut potato browning. Ascorbic acid inhibits the browning mainly by reducing quinones back to phenolic compounds, but L‐cysteine inhibits the browning mainly by decreasing PPO and POD activities.
Efficacy of the long‐acting gonadotropin‐releasing hormone agonist long protocol on IVF/ICSI outcomes of patients with repeated implantation failure
Authors: Chen Xuemei , Zhang Wei , Xu Yanping , Li Wenshu , Wang Xiuzhu , Shi Shulei , Liu Xuemei
Published: October 2023

Objective

The present study aimed to investigate the effect of long‐acting gonadotropin‐releasing hormone agonist (GnRHa) long protocol on in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) outcomes of patients with repeated implantation failure (RIF).

Methods

The present study was carried out from June 1, 2016 to June 30, 2021. A total of 665 patients with RIF were enrolled into the study and classified by the ovarian stimulation protocols. The outcome parameters were compared in each group. In addition, we evaluated the expression of homeobox A10 (HOXA10), integrin β3 and leukemia inhibitory factor (LIF) in endometrial tissues between groups by quantitative RT‐PCR.

Results

Patients who received the long‐acting GnRHa long protocol had significantly higher clinical pregnancy rates (58.0%, 41.7% and 39.9%, respectively; P = 0.008 and 0.003), implantation rates (38.1%, 30.3%, and 30.1%, respectively; P = 0.001 and <0.001) and live birth rates (50.3%, 36.3%, and 31.3%, respectively; P = 0.020 and 0.002) compared with the short‐acting GnRHa long protocol and GnRH antagonist protocol. In addition, we found that long‐acting GnRHa could improve the expression of HOXA10 (P < 0.05).

Conclusion

The long‐acting GnRHa long protocol could improve endometrial receptivity and IVF/ICSI clinical outcomes of RIF patients compared with the short‐acting GnRHa long protocol and GnRH antagonist protocol.
Trends in and outcomes of delivery hospitalizations with lupus and antiphospholipid syndrome
Authors: Lopez Ashley , Wen Timothy , Patel Naomi , Booker Whitney A. , D'Alton Mary E. , Friedman Alexander M.
Published: October 2023

Objective

To assess trends and outcomes associated with systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS) during US delivery hospitalizations.

Study Design

The National Inpatient Sample from 2000 to 2019 was used for this repeated cross‐sectional analysis. We identified delivery hospitalizations with and without SLE. Temporal trends in SLE during delivery hospitalizations were determined using joinpoint regression. Adjusted logistic regression models accounting for demographic, clinical, and hospital factors were used to determine adjusted odds ratios (aORs) for adverse outcomes based on the presence or absence of SLE.

Results

Of an estimated 76 698 775 delivery hospitalizations identified in the NIS, 79386 (0.10%) had an associated diagnosis of SLE. Over the study period, SLE increased from 6.7 to 14.6 cases per 10 000 delivery hospitalizations (average annual percent change 4.5%, 95% CI 4.0–5.1). Deliveries with SLE had greater odds of non‐transfusion severe morbidity (aOR 2.21, 95% CI 2.00, 2.44) and underwent a larger absolute increase in morbidity risk over the study period. SLE was associated with a range of other adverse outcomes including preterm delivery, eclampsia, cesarean delivery, and blood transfusion.

Conclusion

The proportion of deliveries to women with SLE has increased over time in the US, and SLE and APS are associated with a broad range of adverse outcomes.
Preoperative hysteroscopy shortened progression‐free survival in advanced FIGO stage in endometrial cancer: Ten year analysis
Authors: Miao Huixian , Zhang Lin , Jiang Yi , Wan Yicong , Yuan Lin , Cheng Wenjun
Published: October 2023

Objective

To investigate the impact of preoperative hysteroscopy on progression‐free survival (PFS) and disease‐specific survival (DFS), and to explore the factors which contribute to poor clinical outcomes between hysteroscopy and dilation and curettage (D&C) in endometrial cancer (EC).

Methods

A retrospective study was designed by collecting data from women diagnosed with EC through hysteroscopy or D&C from January 2010 to December 2019 in a tertiary hospital in China. A propensity score was used for 1:1 matching of advanced stage patients. Univariate and multivariate analysis were conducted to determine whether hysteroscopy was a prognostic factor in EC and to identify factors associated with its impact on PFS and DFS in different subgroups.

Results

Overall, 543 and 272 women who underwent D&C and hysteroscopy, respectively were included. Compared to D&C, preoperative hysteroscopy was related to reduced PFS and DFS, with a hazard ratio (HR) of 1.904 and 3.905, respectively. Hysteroscopy contributed to an increased risk of positive wash cytology (48.27% vs 24.13%), recurrence (48.28% vs 20.69%) and shorter PFS after matching in FIGO Stage I–IV EC, while there was no significance in positive ascites cytology (14.04% vs 13.45%), PFS and DFS in FIGO Stage I EC.

Conclusions

Hysteroscopy was an independent predictive factor for poor prognosis in EC. Hysteroscopy appeared to be a safe diagnostic method as D&C in FIGO Stage I EC but was a risk factor for increased recurrence and reduced PFS in advanced stage disease. Its impact on DFS is uncertain.
External iliac arterial dissection after robot‐assisted radical cystectomy with an intracorporeal ileal conduit and extended pelvic lymph node dissection
Authors: Nakashima Syunsuke , Hata Shinro , Shinohara Mayuka , Ando Tadasuke , Shin Toshitaka , Mimata Hiromitsu
Published: October 2023

Introduction

External iliac arterial dissection after robot‐assisted laparoscopic procedures is an extremely rare complication. It may cause severe adverse outcomes, such as lower limb necrosis.

Case presentation

A 73‐year‐old man was diagnosed with cT2 ≤ N0M0 bladder cancer and underwent robot‐assisted radical cystectomy. After surgery, he complained of severe left lower leg pain. Computed tomography showed external iliac arterial occlusion. Furthermore, the emergency operation revealed external iliac arterial dissection and occlusion.

Conclusion

The robot arm does not have any sense of force or touch. Thus, it is necessary to pay sufficient attention to the traction of blood vessels and contact with major organs.
A case of bladder cancer after bilateral lung transplantation following bone marrow transplantation
Authors: Arai Yutaro , Goto Yusuke , Sazuka Tomokazu , Fujimoto Ayumi , Sato Hiroaki , Imamura Yusuke , Sakamoto Shinichi , Ota Masayuki , Ikeda Jun‐ichiro , Ichikawa Tomohiko
Published: October 2023

Introduction

The incidence of bladder cancer following transplantation is high; however, no previous studies have reported the development of bladder cancer following bone marrow and bilateral lung transplantations.

Case presentation

A 42‐year‐old man who was followed for bilateral lung transplantation due to chronic graft‐versus‐host disease following bone marrow transplantation complained of gross hematuria. Transurethral resection of the bladder tumor was performed for cT1N0M0 bladder cancer. On the following night, he experienced severe respiratory failure and was intubated. He was discharged on postoperative day 32 with the introduction of home oxygen therapy. The pathological diagnosis was invasive urothelial carcinoma, high‐grade, pT1, with urothelial carcinoma in situ. Further treatment could not be performed because of his poor performance status and immunosuppressive state.

Conclusion

Vigorous screening for bladder cancer coexisting with other malignancies should be performed for transplant recipients for the early diagnosis and prompt treatment of a relatively aggressive bladder cancer.
Systematic approach to localisation of lameness in the distal limb of horses
Authors: Fiske‐Jackson Andy
Published: October 2023

Background: Lameness examination is commonly required in equine veterinary practice, whether it's to investigate a lameness already identified by the owner, or as part of the investigation of poor performance.

Aim of the article: This article outlines a systematic approach to adopt when presented with a lame horse. Although it focuses on examination of the distal limb, the same principles apply when examining the proximal limb.
Pharmacodynamics and Pharmacokinetics of the Profens: Enantioselectivity, Clinical Implications, and Special Reference to S(+)‐Ibuprofen
Authors: Evans Allan M.
Published: October 2023

The 2‐arylpropionic acid derivatives, or “profens,” are an important class of nonsteroidal antiinflammatory drugs (NSAIDs) that have been in clinical use for almost 30 years. Widely used members of this drug class include naproxen, ibuprofen, ketoprofen, flur‐biprofen, and tiaprofenic acid. With the exception of S‐naproxen, the profens have until recently been used clinically as racemic agents, and a “single enantiomer versus racemate” debate has emerged. Several important issues should be considered in the debate: the antinociceptive activity of the R‐enantiomer of at least one profen (flurbipro fen), the possible role of cyclooxygenase (COX)‐independent properties of the R‐enantiomers in the gastrointestinal toxicity of the racemates, the increase in the formation of potentially immunogenic drug‐protein adducts when racemates are administered, and the likelihood that the use of racemates increases the propensity of the profens to alter the pharmacokinetics of other drugs. This review will demonstrate how the use of individual enantiomers can improve understanding of the mechanisms by which the profens elicit their biologic effects.
Evaluation of pharmacist impact on a multidisciplinary transitions of care service in Bundled Payments for Care Improvement Advanced model patients
Authors: Butler Tasha A. , Heiman Elise , Bianco Jessica , Blanco Delilah , Carris Nicholas W. , Martinez Amanda
Published: October 2023

Introduction

Recent evidence shows pharmacist interventions on transitional care teams may reduce 30‐ and 90‐day readmissions.

Objectives

The objective of this study was to evaluate the impact of a virtual multidisciplinary transitional care team including pharmacy services provided to Bundled Payment for Care Improvement Advanced (BPCI‐A) model patients.

Methods

This pre–post implementation retrospective cohort study included adult BPCI‐A patients with traditional Medicare and at least one of eight selected diagnosis‐related groups as the principal admitting diagnosis (sepsis, renal failure, stroke, seizure, urinary tract infection, cellulitis, chronic obstructive pulmonary disease, or pneumonia). The pre‐implementation time period was July 2021 through September 2021, and the post‐implementation time period was November 2021 through March 2022. The primary outcome was the difference between unplanned 90‐day revisits among BPCI‐A patients who received care from the multidisciplinary transitional care team (including pharmacy) versus patients receiving no care from the multidisciplinary transitional care team.

Results

Overall, patients (n = 201) were elderly (mean age ~ 73 years), evenly split male/female (51%), and Caucasian (~73%). Sepsis was the most common principal diagnosis pre‐implementation (n = 26; 28%) and stroke was the most common principal diagnosis post‐implementation (n = 33, 31%). Elixhauser comorbidity index was similar between cohorts. Pre‐implementation, 32% of patients (n = 29) had an unplanned revisit within 90 days versus 27% (n = 28) post‐implementation (p = 0.453). Pre‐implementation, 18% of patients experienced a 30‐day unplanned revisit versus 19% of patients post‐implementation (p = 0.890). The average length of stay for unplanned revisits was 7.4 days in the pre‐implementation cohort versus 8.2 days in the post‐implementation cohort (p = 0.846).

Conclusion

No difference was identified in revisits pre‐ versus post‐implementation. The study may have been impacted by seasonal variation or small sample size as a 5% absolute decrease in revisits is clinically meaningful. Larger and longer studies to optimize readmission prevention strategies are needed.
A case of fulminant type 1 diabetes masquerading acute pancreatitis
Authors: Matsuura Naoki , Yoshino Shumpei , Morisaki Hiroko
Published: October 2023

Fulminant type 1 diabetes is a novel and life‐threatening subtype of type 1 diabetes characterized by its markedly abrupt onset and hyperglycemia with a relatively low glycated hemoglobin level at the onset. We herein describe a typical case of fulminant type 1 diabetes who presented with abdominal pain and vomiting, and whose laboratory test revealed elevated pancreatic enzymes. He was initially diagnosed with acute pancreatitis, but occult and prolonged hyperglycemia eventually led to a diagnosis of fulminant type 1 diabetes.
Machine learning reveals PANoptosis as a potential reporter and prognostic revealer of tumour microenvironment in lung adenocarcinoma
Authors: Han Chunyan , Danzeng Quzhen , Li Liang , Bai Shanwang , Zheng Cuixia
Published: October 2023

Lung adenocarcinoma (LUAD), a prominent lung cancer subtype, has an underexplored relationship with PANoptosis, a recently discovered mode of tumour cell death. This study incorporated iron death, copper death, scorch death, necrotizing apoptosis and bisulfide death into a pan‐death gene set (PANoptosis) and conducted single‐cell analysis of scRNA‐seq data from 11 LUAD samples. Differentially expressed genes were identified, and Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were performed. Univariate COX regression and least absolute shrinkage and selection operator (LASSO) regression were used to screen PANoptosis key genes for constructing an LUAD risk model. The model’s prognostic performance was evaluated using survival curves, risk scores and validation in the Gene Expression Omnibus database. The study also explored the correlation between risk scores, tumour biological function, immunotherapy, drug sensitivity and immune infiltration. The SMS gene in the PANoptosis model was silenced in two LUAD cell lines for cellular validation. Single‐cell analysis revealed eight major cell types and several PANoptosis genes significantly associated with LUAD survival. The risk model demonstrated strong prognostic performance and association with immune infiltration, suggesting PANoptosis involvement in LUAD tumour immunity. Cellular validation further supported these findings. The PANoptosis key risk genes are believed to be closely related to the tumour microenvironment and immune regulation of LUAD, potentially providing valuable insights for early diagnosis and clinical treatment, and broader applications in other tumours and complex diseases.
Hepatic artery protection using a polyglycolic acid sheet during pancreaticoduodenectomy: A multicenter study
Authors: Lee Jun Suh , Yoon Young Chul , Hong Tae Ho , Yoon Yoo‐Seok , Park Sung Eun
Published: October 2023

Background

Postpancreatectomy hemorrhage (PPH) is the most feared complication after pancreaticoduodenectomy (PD). The most common cause is erosion of the gastroduodenal artery stump. Preventive measures have been previously reported, but a consensus is lacking. The aim of this study was to analyze the preventive effect of reinforcing the hepatic artery using a polyglycolic acid (PGA) sheet during PD.

Methods

A multicenter retrospective study was performed, collecting data from three tertiary hospitals in Korea. Patients receiving PD from January 2016 to December 2021 were included. The primary endpoint was rate of PPH from the hepatic artery. Arterial reinforcement (AR) was performed by wrapping the artery with Neoveil (Gunze Ltd) and applying fibrin glue. The perioperative data of patients who did not receive AR were compared with data of those who received AR.

Results

A total of 904 patients were analyzed. The rate of PPH from the hepatic artery was significantly lower in the AR group. (3.5% vs 0.7%, p = .002) In patients with CR‐POPF, the 90 day mortality rate of the AR group was less than half that of the non‐AR group (7.2% vs 3.5%, p = .455) Risk factor analysis showed CR‐POPF to be an independent risk factor for PPH. Arterial reinforcement was shown to be a strong protective factor for PPH (OR 0.20, 95% CI: 0.05–0.72, p = .014).

Conclusions

AR of the hepatic artery using Neoveil and fibrin glue is a simple method that greatly reduces the rate of PPH after PD.
Timing of prophylactic antibiotics administration and suspected systemic infection after percutaneous biliary intervention
Authors: Im Hyunjae , Oh Seung‐Young , Lim Leerang , Lee Hannah , Kwon Jina , Ryu Ho Geol
Published: October 2023

Background/Purpose

Prophylactic antibiotics administration before percutaneous biliary intervention (PBI) is currently recommended, but the underlying evidence is mostly extrapolated from prophylactic antibiotics before surgery. The aim of this study was to evaluate the impact of prophylactic antibiotics administration timing on the incidence of suspected systemic infection after PBI.

Methods

The incidence of suspected systemic infection after PBI was compared in patients who received prophylactic antibiotics at four different time intervals between antibiotics administration and skin puncture for PBI. Suspected post‐intervention systemic infection was assessed according to predetermined clinical criteria.

Results

There were 98 (21.6%) suspected systemic infections after 454 PBIs in 404 patients. There were significant differences among the four groups in the incidence of suspected systemic infection after the intervention (p = .020). Fever was the most common sign of suspected systemic infection. Administration of prophylactic antibiotics more than an hour before PBI was identified as an independent risk factor of suspected systemic infection after adjusting for other relevant factors (adjusted odds ratio = 10.54; 95% confidence interval, 1.40–78.86).

Conclusions

The incidence of suspected systemic infection after the PBI was significantly lower when prophylactic antibiotics were administered within an hour before the intervention.
Association between methicillin‐resistant Staphylococcus aureus nasal carriage and infection after pancreatic surgery
Authors: Jinushi Koichi , Shimizu Junzo , Yamashita Masafumi , Odagiri Kazuki , Yanagimoto Yoshitomo , Takeyama Hiroshi , Suzuki Yozo , Ikenaga Masakazu , Imamura Hiroshi , Dono Keizo
Published: October 2023

Background

Methicillin‐resistant Staphylococcus aureus (MRSA) infections after pancreatectomy are relatively rare; however, they can be fatal when associated with pseudoaneurysms. For the past 12 years, we have been investigating nasal MRSA carriage by polymerase chain reaction testing, postoperatively in patients admitted to the intensive care units, to prevent nosocomial infections. Here, we investigated the relationship between MRSA nasal carriage and postoperative MRSA infection at the surgical site, following pancreatectomy.

Methods

This single‐center retrospective study analyzed 313 pancreatectomies (220 pancreaticoduodenectomies and 93 distal pancreatectomies), performed at our hospital between January 2011 and June 2022. The incidence of surgical site infection (SSI) and postoperative MRSA infection were compared between the nasal MRSA‐positive and nasal MRSA‐negative groups.

Results

MRSA nasal carriage was identified in 24 cases (7.6%), and the frequency of SSIs in the nasal MRSA‐positive and MRSA‐negative groups were 50% and 36.7%, respectively, with no significant difference (p = .273). However, the frequency of MRSA infection among the SSI cases was significantly higher in the nasal MRSA‐positive group (16.7%) than in the nasal MRSA‐negative group (1.7%) (p = .003).

Conclusion

It should be noted that MRSA carriers have a significantly higher frequency of MRSA‐positive SSIs.
Benefit of living donor liver transplantation in graft survival for extremely high model for end‐stage liver disease score ≥35
Authors: Yun Sang Oh. , Kim Jongman , Rhu Jinsoo , Choi Gyu‐Seong , Joh Jae‐Won
Published: October 2023

Background and Aims

Living liver donation with high model for end‐stage liver disease (MELD) score was discouraged despite organ shortage. This study aimed to compare graft survival between living donor liver transplantation (LDLT) and deceased donor liver transplantation (DDLT) recipients with extremely high‐MELD (score of ≥35).

Methods

Between 2008 and 2018, 359 patients who underwent liver transplantation with a MELD score ≥35 were enrolled. We compared graft survival between LDLT and DDLT after propensity score matching (PSM) and performed subgroup analysis according to donor type.

Results

After PSM, there was no statistical difference in graft survival between the LDLT and DDLT groups (p = .466). Old age, acute on chronic liver failure, re‐transplantation, preoperative intensive care unit stay and red blood cell (RBC) transfusion during the operation were risk factors for graft failure (p = .046, .005, .032, .015 and .001, respectively). Biliary complications were more common in the LDLT group (p = .021), while viral infection, postoperative uncontrolled ascites, and postoperative hemodialysis were more common in the DDLT group (p = .002, .018, and .027, respectively). In the LDLT group, acute chronic liver failure, intraoperative RBC transfusion, and early postoperative complications were risk factors for graft failure (p = .007, <.001, and .001, respectively).

Conclusion

Our study showed that LDLT is not inferior to DDLT in graft survival if appropriate risk evaluation is performed in cases of extremely high‐MELD scores. This result will help overcome organ shortages in high‐MELD liver transplantation.
Humoral and cellular immune responses in fully vaccinated individuals with or without SARS‐CoV‐2 breakthrough infection: Results from the CoV‐ADAPT cohort
Authors: Hollstein Moritz M. , Dierks Sascha , Schön Michael P. , Bergmann Armin , Abratis Anna , Eidizadeh Abass , Kaltenbach Sarah , Schanz Julie , Groß Uwe , Leha Andreas , Kröger Andrea , Andag Reiner , Zautner Andreas E. , Fischer Andreas , Erpenbeck Luise , Schnelle Moritz
Published: October 2023

Despite recent advances in prophylactic vaccination, SARS‐CoV‐2 infections continue to cause significant morbidity. A better understanding of immune response differences between vaccinated individuals with and without later SARS‐CoV‐2 breakthrough infection is urgently needed. CoV‐ADAPT is a prospective long‐term study comparing humoral (anti‐spike‐RBD‐IgG, neutralization capacity, avidity) and cellular (spike‐induced T‐cell interferon‐γ [IFN‐γ] release) immune responses in individuals vaccinated against SARS‐CoV‐2 at four different time points (three before and one after third vaccination). In this cohort study, 62 fully vaccinated individuals presented with SARS‐CoV‐2 breakthrough infections vs 151 without infection 3–7 months following third vaccination. Breakthrough infections significantly increased anti‐spike‐RBD‐IgG (p < 0.01), but not spike‐directed T‐cell IFN‐γ release (TC) or antibody avidity. Despite comparable surrogate neutralization indices, the functional neutralization capacity against SARS‐CoV‐2—assessed via a tissue culture‐based assay—was significantly higher following breakthrough vs no breakthrough infection. Anti‐spike‐RBD‐IgG and antibody avidity decreased with age (p < 0.01) and females showed higher anti‐spike‐RBD‐IgG (p < 0.01), and a tendency towards higher antibody avidity (p = 0.051). The association between humoral and cellular immune responses previously reported at various time points was lost in subjects after breakthrough infections (p = 0.807). Finally, a machine‐learning approach based on our large immunological dataset (a total of 49 variables) from different time points was unable to predict breakthrough infections (area under the curve: 0.55). In conclusion, distinct differences in humoral vs cellular immune responses in fully vaccinated individuals with or without breakthrough infection could be demonstrated. Breakthrough infections predominantly drive the humoral response without boosting the cellular component. Breakthrough infections could not be predicted based on immunological data, which indicates a superior role of environmental factors (e.g., virus exposure) in individualized risk assessment.
Association between missing teeth number and all‐cause and cardiovascular mortality: NHANES 1999–2004 and 2009–2014
Authors: Shen Ruming , Chen Shuaijie , Shen Jiayi , Lv Lingchun , Wei Tiemin
Published: October 2023

Background

The association between tooth loss and all‐cause and cardiovascular mortality requires further investigation.

Methods

This study included 17993 participants from the National Health and Nutrition Examination Surveys (NHANES) 1999–2004 and 2009–2014. Weighted multivariable Cox proportional hazard models were used to assess the association between tooth loss and all‐cause and cardiovascular mortality. Restricted cubic splines (RCS) were incorporated in the models to explore potential nonlinear relationships.

Results

Over a median follow‐up of 116 months, 2152 participants died, including 625 cardiovascular deaths. Compared to participants without missing teeth, participants with 11–19 missing teeth had the highest risk of all‐cause mortality (hazard ratio [HR] 1.89, 95% confidence interval [CI] 1.43–2.51), while participants with 6–10 missing teeth had the highest risk of cardiovascular mortality (HR 2.51, 95% CI 1.68–3.76). RCS analyses revealed nonlinear associations between number of missing teeth and all‐cause (p < 0.001) and cardiovascular (p = 0.001) mortality. With < 10 missing teeth, each additional missing tooth increased all‐cause and cardiovascular mortality by 6% (HR 1.06, 95% CI 1.03–1.09) and 9% (HR 1.09, 95% CI 1.03–1.15), respectively. However, when the number of missing teeth was ≥10, the risk of mortality did not continue to increase with more missing teeth. A significant interaction was found between tooth loss and age (p < 0.001 for both outcomes).

Conclusion

We observed an inverted L‐shaped association between tooth loss and mortality, wherein risks increased with more missing teeth until 10, but did not continue increasing thereafter. The association was stronger in adults < 65 years old.
Ferroelectric liquid crystal array driven by a two‐layer electrode with a 1 × 1 μm pixel pitch for light modulation in electro‐holography
Authors: Aso Shintaro , Yamamoto Kisho , Aoshima Ken‐ichi , Higashida Ryo , Funabashi Nobuhiko , Shibasaki Junichi , Ishinabe Takahiro , Shibata Yosei , Fujikake Hideo , Machida Kenji
Published: October 2023

We clarified that a ferroelectric liquid crystal (FLC) has high resolution display capability as small as 1 × 1 μm pixel pitch using an FLC pixel array with a two‐layer electrode, which has a 1 × 1‐μm‐checkered apertured electrode and a plane electrode separated by an insulation layer. By applying +2 V to the apertured electrode and −10 V to the plane electrode in the two‐layer electrode and 0 V to the transparent common electrode, a checkered pattern was clearly observed, which indicates the successful individual pixel driving with a pixel pitch of 1 × 1 μm. When fabricating 1 × 2‐μm‐pitch rectangular FLC pixels, we elucidated that the liquid crystal alignment direction should be along the shorter side of the pixels to avoid asymmetric transmittance distribution in each pixel. Moreover, we successfully reconstructed a 3D holographic image using 10 × 10 k FLC pixel array with a pitch of 1 × 1 μm driven by the two‐layer electrode with hologram‐patterned apertures. We showed that FLC is a strong candidate material for realizing spatial light modulator with extremely small pixel pitches, which is essential for holographic displays with wide‐viewing‐zone angles.
A novel heterozygous deletion in ABCB4 gene in a Chinese family with intrahepatic cholestasis of pregnancy, neonatal hyperbilirubinemia, and cholelithiasis: Case reports and literature review
Authors: Zheng Yang , Rao Qunfang , Han Yiru , He Jianqin
Published: October 2023

Background

ABCB4 gene (OMIM *171060) variant is associated with a wide clinical spectrum of hepatobiliary diseases, including familial intrahepatic cholestasis of pregnancy (ICP), progressive familial intrahepatic cholestasis type 3 (PFIC3), and neonatal hyperbilirubinemia due to impaired protection of the bile duct. The majority of reported cases, however, were missense or nonsense variants, with few deletion variant findings in the Chinese population.

Method

We performed whole genome sequencing and confirmed it with Sanger sequencing of the proband infant and his families. Clinical courses and laboratory results were documented and collected from the proband infant and his mother. We also reviewed other published cases related to genetic variants in ABCB4 in the Chinese population.

Results

A 26‐year‐old Chinese female (II.2) who had recurrent intrahepatic cholestasis of pregnancy and her 49‐day‐old son (III.4) who had hyperbilirubinemia, both presented with extremely elevated total bile acid, cholestatic dominant pattern liver function abnormalities. They were able to stay relatively stable with mild pruritus on ursodeoxycholic acid treatment. After ruling out other possibilities, genetic sequencing revealed a diagnosis of heterozygous deletion variant NM_018849.3:c.1452_1454del (NP_061337.1:p.Thr485del) in ABCB4, which was not reported before, in the symptomatic mother (II.2), index patient (III.4), and the symptomatic grandmother (I.2). This variant resulted in clinical spectrums of ICP, neonatal hyperbilirubinemia, and cholelithiasis in our pedigree.

Conclusion

We reported a novel heterozygous deletion variant of the ABCB4 gene in a Chinese family, as well as a literature review of ABCB4‐related disorders. We aim to facilitate healthcare professionals to better understand genetic factors as an uncommon cause of hepatobiliary diseases, as well as improve therapeutic strategies in challenging clinical situations such as pregnancy and neonatal care.
Robust ∞ model reduction for the continuous fractional‐order two‐dimensional Roesser system: The 0 < ε ≤ 1 case
Authors: Zhang Jia‐Rui , Lu Jun‐Guo
Published: October 2023

This study analyzes the model reduction methods and the robust model reduction methods for the continuous fractional‐order (FO) two‐dimensional (2D) Roesser system with the FO ranging from 0 to 1. A sufficient LMI‐based condition is given by Projection Lemma, the FO‐stable‐region‐analyze method and matrix analysis, guaranteeing that the error system is stable and that its transfer function's ‐norm is bounded. Then, the approach to design the reduced‐model system of the original continuous FO 2D Roesser model is given. The robust model reduction methods for continuous FO 2D Roesser systems with polytopic uncertainties are proposed based on the results above. In the end, two numerical examples are used to demonstrate the effectiveness of the results.
HyperSLICE: HyperBand optimized spiral for low‐latency interactive cardiac examination
Authors: Jaubert Olivier , Montalt‐Tordera Javier , Knight Daniel , Arridge Simon , Steeden Jennifer , Muthurangu Vivek
Published: October 2023

Purpose

Interactive cardiac MRI is used for fast scan planning and MR‐guided interventions. However, the requirement for real‐time acquisition and near‐real‐time visualization constrains the achievable spatio‐temporal resolution. This study aims to improve interactive imaging resolution through optimization of undersampled spiral sampling and leveraging of deep learning for low‐latency reconstruction (deep artifact suppression).

Methods

A variable density spiral trajectory was parametrized and optimized via HyperBand to provide the best candidate trajectory for rapid deep artifact suppression. Training data consisted of 692 breath‐held CINEs. The developed interactive sequence was tested in simulations and prospectively in 13 subjects (10 for image evaluation, 2 during catheterization, 1 during exercise). In the prospective study, the optimized framework—HyperSLICE— was compared with conventional Cartesian real‐time and breath‐hold CINE imaging in terms quantitative and qualitative image metrics. Statistical differences were tested using Friedman chi‐squared tests with post hoc Nemenyi test (p < 0.05).

Results

In simulations the normalized RMS error, peak SNR, structural similarity, and Laplacian energy were all statistically significantly higher using optimized spiral compared to radial and uniform spiral sampling, particularly after scan plan changes (structural similarity: 0.71 vs. 0.45 and 0.43). Prospectively, HyperSLICE enabled a higher spatial and temporal resolution than conventional Cartesian real‐time imaging. The pipeline was demonstrated in patients during catheter pull back, showing sufficiently fast reconstruction for interactive imaging.

Conclusion

HyperSLICE enables high spatial and temporal resolution interactive imaging. Optimizing the spiral sampling enabled better overall image quality and superior handling of image transitions compared with radial and uniform spiral trajectories.
Outcomes after metabolic and bariatric surgery in preteens versus teens using the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program database and center‐specific data
Authors: Shah Adil , Liang Norah E. , Bruzoni Matias , Pratt Janey S. A. , Zitsman Jeffrey , Nadler Evan P.
Published: October 2023

Objective

The American Academy of Pediatrics (AAP) recently released clinical guidelines for the treatment of childhood obesity, including surgery being appropriate for children 13 years of age and older. The use of this age cut‐off was due to a lack of data for children younger than 13. To address this knowledge gap, the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program (MBSAQIP) database was queried to compare outcomes in preteens to teens after bariatric surgery hypothesizing that there would be no difference in outcomes between the two groups.

Methods

Patients from the MSAQIP database (2016–2021) were identified and divided into groups <13 years and 13–18 years and were matched using propensity scores based on race, sex, and preoperative BMI. Outcomes were compared including change in BMI, complication rates, 30‐day readmission or reoperation, and mortality. Additionally, the centers responsible for the bulk of the preteen patient entries queried their center‐specific databases to evaluate weight loss over time.

Results

A total of 4755 patients were identified, 47 of whom were <13 years of age. Preteens had similar sex distribution (66% vs. 75% female), were more likely to be Black (27.7% vs. 18.3%) or Hispanic (21.3% vs. 7.6%) race, and weighed less (274 ± 58 vs. 293 ± 85 lb, p = 0.01), but they had similar BMI (46.9 ± 7 vs. 47 ± 13 kg/m2) as their teen counterparts. Preteens were more likely to suffer from sleep apnea (34% vs. 19%, p < 0.01) and insulin‐dependent type 2 diabetes (10.6% vs. 1.8%, p < 0.01). There were no complications in the preteens compared to teens (0% vs. 0.5%), and they did not undergo any unplanned readmissions (0% vs. 2.9%) or reoperations (0% vs. 0.8%) within 30 days of surgery. There were also no mortalities reported in preteens (0% vs. 0.1%). The risk‐adjusted decrease in BMI between preteens and teens was also comparable at 30 days (4.2 [95% CI: 3.0–5.4] vs. 4.6 [95% CI: 4.4–4.7], p = 0.6). Decrease in BMI in preteens was 7 ± 3 kg/m2 at 3 months and 9 ± 4 kg/m2 at 12 months after surgery, which represented a percentage BMI change of 16 ± 7 and 20 ± 8, respectively.

Conclusions

This study demonstrates that bariatric surgery in preteens is safe and efficacious when performed at specialized centers, and that age criteria may not be required. The AAP and others are encouraged to include age cut‐offs in their guidelines for children with obesity and bariatric surgery only when data are available to support their inclusion.
Generative learning‐based model for the prediction of 2D stress distribution
Authors: Gulakala Rutwik , Markert Bernd , Stoffel Marcus
Published: October 2023

In this study, we introduce a Generative learning‐based approach to accelerate Finite Element simulations. The aim is to explore the ability of a Generative learning‐based approach to predict the output of Finite Element simulations. Often, the drawback of classical regression models is that they are bound to the distribution of training data and cannot extrapolate outside of the training domain. In the current study, to overcome this, we propose a Generative Adversarial Network (GAN) based approach for learning to infer structural mechanics simulations. GANs have the ability to learn the underlying distribution of data and can efficiently extrapolate outside the training range. We train the proposed network on data obtained from classical Finite Element simulations based on linear elastic and Johnson‐Cook plasticity models. The goal here is to understand the ability of a GAN to replace FEM by incorporating the underlying mechanics knowledge into the network to enhance the generalizing ability of the network for various materials on various loading and boundary conditions. We propose an encoder‐decoder‐like U‐Net generator architecture with activated skip connections and a PatchGAN‐based discriminator that discriminates based on local patches of data leading to a more robust critique for the generator. The advantage of the proposed framework is that it takes inputs such as the nodal information, their corresponding edges, nodal coordinates and the boundary conditions for each particular node from a Finite Element pre‐processor and computes the von Mises stress at each node as output that can be read by a Finite Element post‐processor. Also, the novelty of the proposed GAN is that, unlike the existing literature, it takes nodal values such as applied Boundary conditions and coordinates as inputs instead of images and performs nonlinear regression with Finite Element data and gives von‐Mises stresses at each node as output.
Using a futures orientation to enable adaptation of protected areas under climate change
Authors: Múnera‐Roldán Claudia , Colloff Matthew J. , van Kerkhoff Lorrae , Andrade German I.
Published: October 2023

Protected areas are central for long‐term conservation of biodiversity and can potentially support climate change mitigation. But protected areas are also affected by climate change. Managers and scientists are increasingly facing the difficult task of making decisions under rapid change. Understanding individual and institutional futures considerations for adaptation is fundamental to evaluate whether protected area governance is adequate to anticipate, prepare and respond to climate change.

Using mixed qualitative methods, we analysed adaptation narratives extracted from 51 semi‐structured interviews with conservation practitioners and scientists involved in protected area management in Australia, Colombia and South Africa. We applied a multidimensional model to examine how people make sense of the concept of adaptation. The model allowed us to evaluate how different actors perceive and conceptualise the future and their level of awareness of climate change impacts on values of protected areas, as reflected in the expectations and motivations behind adaptation actions.

The results show a plurality of adaptation concepts and approaches. The narratives are framed under different governance approaches (top‐down, bottom‐up, participatory) influencing the sense of agency, the rationale for adaptation (adaptation of what and for whom) and the level of acceptance of change. Action time is associated with preferences and actions in response to ecological change, with more proactive action linked with systemic approaches.

We propose that examining world views underpinning how individuals and institutions make sense of the concept of adaptation can support future‐oriented conservation practices despite the inherent uncertainty of climate change. The narratives presented here may provide a basis to facilitate deliberations about current practices and identify potential contradictions between individual and collective aspirations for adaptation to create pathways for collective action towards desired futures.

Read the free Plain Language Summary for this article on the Journal blog.
Transcriptomics and proteomics reveal distinct biology for lymph node metastases and tumour deposits in colorectal cancer
Authors: Brouwer Nelleke PM , Webbink Loth , Haddad Tariq S , Rutgers Natasja , van Vliet Shannon , Wood Colin S , Jansen Pascal WTC , Lafarge Maxime W ,   imCMS Consortium, de Wilt Johannes HW , Hugen Niek , Simmer Femke , Jamieson Nigel B , Tauriello Daniele VF , Kölzer Viktor H , Vermeulen Michiel , Nagtegaal Iris D
Published: October 2023

Both lymph node metastases (LNMs) and tumour deposits (TDs) are included in colorectal cancer (CRC) staging, although knowledge regarding their biological background is lacking. This study aimed to compare the biology of these prognostic features, which is essential for a better understanding of their role in CRC spread. Spatially resolved transcriptomic analysis using digital spatial profiling was performed on TDs and LNMs from 10 CRC patients using 1,388 RNA targets, for the tumour cells and tumour microenvironment. Shotgun proteomics identified 5,578 proteins in 12 different patients. Differences in RNA and protein expression were analysed, and spatial deconvolution was performed. Image‐based consensus molecular subtype (imCMS) analysis was performed on all TDs and LNMs included in the study. Transcriptome and proteome profiles identified distinct clusters for TDs and LNMs in both the tumour and tumour microenvironment segment, with upregulation of matrix remodelling, cell adhesion/motility, and epithelial–mesenchymal transition (EMT) in TDs (all p < 0.05). Spatial deconvolution showed a significantly increased abundance of fibroblasts, macrophages, and regulatory T‐cells (p < 0.05) in TDs. Consistent with a higher fibroblast and EMT component, imCMS classified 62% of TDs as poor prognosis subtype CMS4 compared to 36% of LNMs (p < 0.05). Compared to LNMs, TDs have a more invasive state involving a distinct tumour microenvironment and upregulation of EMT, which are reflected in a more frequent histological classification of TDs as CMS4. These results emphasise the heterogeneity of locoregional spread and the fact that TDs should merit more attention both in future research and during staging. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.